1984 vimal sleep research

8/11/2019 1984 Vimal Sleep Research

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Brain Research,

298 (1984) 75-90 75

E ls ev ie r

S l e e p a n d P u r p o s iv e B e h a v io r : I n v e rs e D e v i a t i o n s F r o m R a n d o m n e s s o f N e u r o n a l F i r in g

P a t te r n s i n t h e F e l in e T h a l a m u s A N e w F o r m o f H o m e o s t a s is ?

T . J. M A R C Z Y N S K I , L . L . B U R N S , G . T . L I V E Z E Y , R . L . P . V I M A L a n d E . C H E N

Department of Pharrnacology, Universityof lllinois at Chicago, College of M edicine, Chicago, IL 60612 U.S.A.)

(A ccep ted Aug ust 30th, 1983)

Key words:

s l eep-wake cycles - - neurona l f i r ing pa t t e rns - - random mode l - - nucleus re t i cu la r i s tha lami - - ca t

In behav ing ca t s t ra ined to p re s s a ba r fo r s ma l l a l iquo t s o f m i lk reward , s ing le neurona l f ir ing pa t t e rns were mo ni to red f rom the nu-

c leus re ti cu la ri s (NR) tha lami dur ing ba r b re s s ing (BP) , s ubs equen t q u ie t wakefu lness wi th E E G s p ind le s (S-QW ), g rooming behav io r

(GR ) and s low-wave s leep (SWS) . T he t empo ra l pa t t e rns in the neu rona l s p ike t ra ins were ana lyzed us ing a non -pa rame t r i c me thod

bas ed on re l a tive re la t ions be tween s equen t i a l s p ike in te rva l s . T he dev ia t ions o f pa t t e rn occur rences f rom the rand om mod e l were

quant i f ied.

Dur ing BP, s pec if ic pa t t e rns occur red much mo re o f t en whi le o the rs occur red much l es s o f t en than p red ic ted by the random mode l .

Pa t t e rns tha t were dom inan t dur ing BP, were s e lec t ive ly s uppres s ed o r v i r tua l ly e l imina ted dur ing S-QW, G R and SW S, des p i t e the

inc reas ed f ir ing ra t e ; and , v ice ve rs a , pa t t e rns tha t were s uppres s ed be low chance l eve l dur ing BP, becam e dom inan t dur ing S-Q W,

GR and SW S. T he magn i tudes o f the s e inve rs ions o f the s t a t i s ti ca l d i s t r ibu t ion o f pa t t e rns were no t random bu t g rade d and pos i t ive ly

corre la ted , thus indicat ing that they were h om eosta t ica l ly control led . Since the invers ions w ere a lre ady evident short ly after the sa-

t i a t ed an ima l ceas ed ba r p re s s ing , they may be re l a t ed to the 'need ' fo r s l eep .

On the bas i s o f the known mechan i sms o f pa t t e rn gen e ra t ion and changes in recep to rs fo r pu ta t ive trans mi t t e r s , it was pos tu la ted

that the invers ions o f pat tern d is t r ibut ion are re la ted to the recu perat ive funct ion of SWS, i . e . resens i t iza t ion of recep tors that had

been des ens i t i zed dur ing the an ima l ' s st e reo typ ic BP pe r fo rmance . T h e N R and o the r neurona l ens embles s eem to cons t i tu te an os c i l-

la tory system w ith two m odes o f rec iprocal connect ivi t ies : one is suppo rt ing wakefulness and em iss ion of specif ic f i ring pat terns , and

the oth er is incom pat ible with wakefulness and ins tead is associa ted with invers ion of s ta t is t ica l dis t r ibut ion of f i r ing pat ter ns and recu-

pera t ive function of SW S.

I N T R O D U C T I O N

T h e i n t u it i v e v i e w i s t h a t s l o w - w a v e s l e e p ( S W S )

r e m o v e s ' w e a r a n d t e a r ' , i . e . th e i r r e l e v a n t p l a s ti c

( m a c r o m o l e c u l a r ) c h a n g e s g e n e r a t e d i n n e u r o n a l

s y s t e m s d u r i n g p u r p o s i v e b e h a v i o r a n d / o r c o g n i t i v e

p r o c e s s e s 11.29. T h e r e i s , h o w e v e r , n o q u a n t i f i a b l e

n e u r o n a l a c t i v i t y s u p p o r t i n g t h i s v i e w b e c a u s e m o s t

n e u r o n s o f th e m a m m a l i a n b r a i n t e n d t o f ir e b o t h

d u r i n g w a k e f u l n e s s a n d S W S 11,20,29,30,36. T h i s i s p a r -

t i c u la r l y t r u e f o r t h e n e u r o n s o f t h e n u c l e u s r e t i c u l a -

r is ( N R ) , i n w h i c h m o s t c e l ls e m i t l o n g , h i g h - f r e q u e n -

c y b u r s t s o f s p i k e s d u r i n g E E G s p i n d l e s a n d d e l t a

w a v e s o f S W S 3,20.30,33,34,36. T h e i n p u t - o u t p u t r e l a -

t i o n s o f t h e N R 9,16.32, t h e a s s o c i a t i o n b e t w e e n N R a c -

t i v it y a n d i n h i b i t i o n o f t h e t h a l a m i c r e l a y n u -

c l e i 12,20,33,34,36, a n d t h e e v i d e n c e t h a t N R n e u r o n s u s e

y - a m i n o b u t y r i c a c i d a s t r a n s m i t t e r 15, s u p p o r t t h e h y -

p o t h e s i s t h a t N R p l a y s a r o l e in a t t e n t i o n b y g a t i n g

s e n s o r y i n p u t t o c o r t e x 32,34, a n d i n m o d u l a t i n g m o t o r

o u t p u t b y e x e r t i n g c o n t r o l o v e r t r a n s m i s s i o n t o c o r -

t e x o f i m p u l s e s f r o m t h e c e r e b e l l u m 12,20.

T h e h e t e r o g e n o u s i n p u t r e c e iv e d b y t h e l o ng d e n -

d r i t e s o f N R n e ur o ns 9 ,3 2 s u g g e s t s t h a t t h e y a r e c a p a -

b l e o f e m i t t i n g a w i d e s p e c t r u m o f f ir i n g p a t t e r n s r e -

l a t e d to b e h a v i o r a l s t a t e s a n d s p e c if i c s o m a - d e n d r i t i c

d i s t r i b u t io n o f s y n a p t i c d r i v e. H e n c e , u n l i k e t h e c o n -

v e n t i o n a l a n a l y s i s b a s e d o n f i ri n g r a te a n d i ts p e r i o d i -

c i ti e s ( e . g . a u t o c o r r e l a t i o n ) , t h e a i m o f th e p r e s e n t

s t u d y is t o a n a l y z e t h e i n t r a b u r s t t e m p o r a l p a t t e r n s o f

a c t i o n p o t en t i a ls e m i t t e d b y t h e N R n e u r o n s d u r i n g

t h e a n i m a l ' s p u r p o s i v e b e h a v i o r , s u c h a s b a r p r e s s in g

Correspondence:

T . J . Marczyns k i , Dep a r tme n t o f Pha rm aco logy , Unive rs i ty o f I l l ino is at Ch icago , Co l l ege o f M edic ine , Ch icago ,

IL 60612 , U . S . A .

0006-8993/84/ 03.00 1984 Else vier Science Pub lishers B.V.


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76

(BP) for mi lk reward, quiet wakefulness af ter sat ia-

t ion (S-QW), and SWS. Our

working hypothesis

is

that the s ta t ist ical dis t r ibut ion of pat terns emit ted

dur ing purpos ive behavior should be inversely re-

la ted to the dis t r ibut ion of the same pat terns dur ing

subsequent quiet wakefulness and SWS. This hy-

pothes is stems f rom the fol lowing backg round , which

is summ arized in the diagram of Fig. 1 bot tom .

First

in ins tances in which the CNS neurons have

been found to r ece ive axona l con tac t s f rom more

than one pathway, each mediated by a di f ferent

t ransmit ter , such synapses are not randomly dis t r ib-

uted on the soma-dendr i tes but are segregated to

well-de fined regions13,z4,2~. M ore ov er, if selective ly

act ivated, each input tends to p roduc e specif ic f i ring

patterns at the axon hillock~3,

Second

the f ir ing pat-

t e rns a r e d e te rmined by many f ac to rs , amon g which

the most imp or tant are the spat ia l d is tr ibut ion of syn-

apt ic dr ive, changes in membrane res is tance and cur-

rent f low betwe en the dend r i tes and the axon hi l lock.

as wel l as the repercuss ive, i .e . re t r ograd e, depolar i -

zing inf luences f rom the axon hi l lock that invade the

soma-dendr i tes fol lowing each act ion potent ia l and

interact with the dendrit ic postsynaptic potentials~.

The n ature of the la t ter in teract ions~ and the m odels

of CNS neurons~ contradict the classic notion that

neuro ns are s imple integrators ; ins tead, they indicate

that neurons may funct ion as coincidence detectors

and gating units .

Third

desens i t izat ion of receptors

for speci f ic t ransmit ters i s known to develop readi ly

upon repet i t ive act ivat ion of speci f ic brain path-

ways ~,38. Mo reo ve r, large (up to 78 ) cha nges in re-

ceptors for most know n putat ive t ransm it ters occur in

behaving animals in relat ion to s leep-wake cy-

cles 1s.19. He nc e, if desensit ization during the anim al 's

long bar p r es sing per fo rmance (BP) does no t deve lop

rando mly, but a t speci f ic soma-d endr i t ic s i tes (owing

to segregat ion of synapses and act ivat ion of speci f ic

. - . . ? ; , ,

.,;..

, .~ . ; ~ . ,~ ,~ : : ~ : . ,

I I , ~ I ~ ? L , , ,,

MO

' ~- ~ *, tND

Fig. 1 . Top: examples of h isto logica l local iza t ion of the e lec t rode t ips in the nuc leus re ticula r is tha lami (R) . Middle : d is t r ibut ion of 32

neuron s f rom which the sp ike t ra in records have b een ana lyzed. O n the basis of the i r f i ring pa t te rns in re la t ion to the anim al s behav-

ior , the neurons have been d iv ided in to 3 groups: 14 slow-wave sleep onse t neuro ns (SWSo), 12 mot or output neuron s (MO) , and 6

indiffe rent neurons ( IN D). Abb revia t io ns for the tha lamic nuc le i: MD, media l is dorsa l is ; CL, centra l is an te r ior ; LP, la te ra l is poste r i -

or ; LD, la te ra lis dorsa l is ; VA, v entra l is an te r ior ; VL, ventra l is la te ral is : VPL, v entra l is poste ro la te ra l is ; CD, cauda te nuc leus. Bot-

tom: two hypothe t ica l s ta tes of the same re t icula r is neuron whose proximal dendri tes show inverse spa t ia l d is t r ibut ion of synapt ic

dr ive (b lack regions) tha t may be res ponsib le for inversion of s ta t i s t ica l d is t r ibut ion of f i r ing pa t te rns dur ing SWS and goa l-d i rec ted be-

havior . The two a rrows a t the axo n h i l lock indica te the impo rtance of the re t rog rade d epola r iz ing inf luences on the genera t ion of f i ring

pa t te rns throug h in te rac ton wi th the den dri t ic synapt ic dr ive .


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p a t h w a y s ) , t h e n , u p o n t e r m i n a t i o n o f B P , t h e p a t -

t e r n s c o n t r o l l e d b y t h e s e r e c e p t o r s s h o u l d n o t o n l y

r e t u r n t o t h e l e v e l o f r a n d o m o c c u r r e n c e , b u t s h o u l d

d r o p b e l o w t h a t l e v el . M o r e o v e r , th e m o m e n t a r y r e -

l a x a t i o n o f c o n s t r a i n t s o f p u r p o s i v e b e h a v i o r a n d

p s e u d o - r a n d o m i n t e r a c t i o n s b e t w e e n n e u r o n a l e n -

s e m b l e s s h o u l d p r o v i d e s y n a p t i c d r i v e s u f f i c i e n t f o r

t h e e m e r g e n c e o f d i f f e r e n t f i r i n g p a t t e r n s d e t e r -

m i n e d b y m o r e e f f e c ti v e r e c e p t o r p a t c h e s , p r e s u m -

a b l y a d j a c e n t t o t h o s e t h a t h a d b e e n d e s e n s i t i z e d .

Thus , an i nve r s i on i n s t a t i s t i ca l d i s t r i bu t i on o f pa t -

t e r n s s h o u l d d e v e l o p . A s s h o w n b e l o w , t h i s w a s i n -

d e e d t h e c a se . P r e l i m i n a r y r e p o r t o f s o m e o f th e d a t a

has be en pub l i s h ed 26.

METHODS

Surgery and record ing

T w e l v e a d u l t c a t s o f e i t h e r s e x w e r e t r a i n e d t o

p r e s s a l e v e r f o r 1 m l o f m i l k r e w a r d w h i c h w a s p r e -

s e n t e d o n a 1 : 7 f i x e d ra t i o s c h e d u l e . T h e a n i m a l s r e -

m a i n e d o n a 2 3 - h f o o d a n d w a t e r d e p r i v a ti o n s c h e d-

u l e . F o l l owi ng t he ba r p res s i ng s es s i on , l a s t i ng 60 --80

m i n , t h e y h a d a d l i b i t u m a c c e s s t o P u r i n a c h o w a n d

w a t e r f o r a b o u t 1 5 m i n u t e s .

T h e s t e r e o t a x i c im p l a n t a t i o n o f th e ' f l o a t i n g ' b u n -

d l e s o f m i c r o e l e c t r o d e s ( 2 5 p m t u n g s t e n w i r e s) f o r

' c h r o n i c ' e x t r a c e l l u l a r r e c o r d i n g o f a c t i o n p o t e n t i a l s ,

a n d t h e p r o c e s s i n g o f t h e d a t a s t o r e d o n m a g n e t i c

t ape , hav e b een p rev i ous l y desc ri bedS,25 ,27 . A na l y zed

s p i k e t ra i n s c o n s i s t e d o f a p p r o x i m a t e l y 1 m s d u r a t i o n

n e g a t i v e - p o s i t i v e o r p o s i t i v e - n e g a t i v e w a v e w i t h re l -

a t i v e l y s l o w ( 0 . 5 m s ) r i s i n g p h a s e , a n d t h e r e f o r e i t

w a s u n l i k e l y t h a t t h e y o r i g i n a t e d f r o m p a s s in g f i b r e s .

I f t h e e l e c t r o d e p i c k e d u p m u l t iu n i t a c t i v i t y , a s p i k e

e n h a n c e r ( H a e r C o . ) a n d t h e w i n d o w a m p l i t u d e d is -

c r i m i na t o r , a s we l l a s t he o s c i l l o s cop i c d i s p l ay o f t he

s h a p e o f t h e a c t i o n p o t e n t i a l d u r i n g t h e e d i t in g o f t h e

da t a , a l l owe d t he i s o l a t i on o f t he s ing l e un i t

spikes25.27.

F o r E E G r e c o r d i n g , st a in l e s s s t e e l s c r e w e l e c r o d e s

w e r e u s e d o v e r t h e p a r i e t o - o c c i p i t a l a n d f r o n t a l c o r -

t e x . A f t e r c o m p l e t i o n o f e x p e r i m e n t s , t h e a n i m a l s

w e r e s a c r if i c e d w i t h a l a r g e d o s e o f s o d i u m p e n t o b a r -

b i ta l , a s m a l l D C c u r r e n t w a s p a s s e d t h r o u g h t h e m i -

c r o e l e c t r o d e s , a n d t h e b r a i n w a s p e f f u s e d w i t h s a li n e

a n d 1 0 f o r m a l d e h y d e . T h e e l e c t r o d e p l a c e m e n t s

w e r e c h e c k e d i n f r o z e n 3 0 p m s e c t i o n s s t a i n e d w i t h

77

c r e s y l e c h t v i o l e t. T h e r e s u l ts a r e b a s e d e x c l u s iv e l y

o n n e u r o n s t h a t w e r e l o c a t e d w i th i n th e 0 . 5 - 1 . 2 m m

b a n d o f t h e N R ( F ig . 1 ) ; t h e y y i e l d e d s p i k e t ra i n s f o r

6 w e l l - d e f i n e d b e h a v i o r a l e p i s o d e s r e c o r d e d d u r i n g

3 - - 5 - h s e s s i o n s : b a r p r e s s i n g ( B P ) , g r o o m i n g ( G R ) ,

s y n c h r o n i z e d q u i e t w a k e f u l n e s s ( S - Q W ) , S W S - 1 , i .e .

w i t h l e ss t han 50 o f de l t a wav es , S W S -2 , i . e . w i t h

m o r e th a n 50 o f d e l ta w a v e s , a n d d e sy n c h r o n i z e d

q u i e t w a k e f u l n es s ( D - Q W ) . T h e E E G c r it e ri a w e r e

thos e e s tab l i shed for cat s 37.

Spik e t ra in analys i s

1) Inequal i ty pat terns

T h e t e m p o r a l p a t t e r n s i n n e u r o n a l s p i k e t r a i n s

w e r e a n a l y z e d u s i n g t h e n o n - p a r a m e t r i c m e t h o d

b a s e d o n r e l a t i v e r e l a t i o n s b e t w e e n s e q u e n t i a l s p i k e

i n t e rva l s5,22,25,27. B rie fly th e sp ike inte rva ls w er e

m e a s u r e d w i t h r e s o l u t i o n o f 0 . 1 m s a n d t h e v a l u e s

w e r e s t o r e d i n s e q u e n t i a l o r d e r . T h e i n t e r v a l s w e r e

c o m p a r e d i n s e q u e n t i a l p a i r s: i f t h e s e c o n d i n t e r v a l i n

a p a i r w a s g r e a t e r o r s m a l l e r t h a n t h e f ir s t o n e , a s ig n

( + o r - - ) w a s e n t e r e d ( r e s p e c t i v e l y ) i n t o s e q u e n t i a l

m e m o r y b in s o f a P D P -1 1 - 45 c o m p u t e r . T h e o c c u r-

r ence o f s i gn 0 r e s u l t i ng f rom ' equa l ' i n t e rva l s , was

l es s t h a n 0 . 5 a n d w a s d i s r e g a r d e d . E a c h ' p h r a s e ' o f

s ig ns w a s t h e n p a r s e d i n t o ' w o r d s ' c o m p o s e d o f 3 - 7

signs.

T h e b e s t d i s t in c t i o n b e t w e e n b e h a v i o r a l s t a te s w a s

a c h i e v e d b y a n a l y z i n g t h e d i s t r ib u t i o n o f t h e h e x a -

g r a m s , i . e. w o r d - p a t t e r n s c o m p o s e d o f 6 i n e q u a l i t y

s ig n s g e n e r a t e d b y 7 sp i k e i n t e rv a l s . T h e h e x a g r a m s

c a n o c c u r i n 6 4 d i f f e r e n t s ig n p e r m u t a t i o n s . T h e a n a l -

y s is o f p e n t a g r a m a n d t r i g r a m p a t t e r s w a s u s e d t o il-

l u s t r a te a p a r t i c u l a r p o i n t . E a c h p a t t e r n h a s a s p e c if ic

t h e o r e t i c a l p r o b a b i l i t y o f o c c u r r e n c e , i f t h e a s s u m p -

t i o n is m a d e t h a t t h e i n t e r v a l s w h i c h g e n e r a t e t h e i n-

e q u a l it y p a t t e r n s a r e r a n d o m a n d / o r i n d e p e n d e n t

f rom on e anot he rS .25 . 27. Thus , fo r each beh av i o ra l

s t at e , t h e c o m p u t e r c o m p a r e d t h e e m p i r ic a l w i th t h e

t h e o r e t i c a l o c c u r r e n c e s o f e a c h p a t t e r n ; t h e d i f f e r -

e n c e s a n d t h e d i r e c t i o n o f d e v i a t i o n f r o m t h e r a n d o m

m o de l we re quan t i f i ed u s i ng ch i - s q ua re s t a t is t i c s 2.

T h e c o m p u t e r p l o t t e d t h e c h i - s q u a r e v a l u e s ( o r d i -

n a t e ) f o r e a c h p a t t e r n ( a b s c i s s a ) w h i c h w e r e p r i n t e d

v e r t i c a l l y , a n d a r e a r r a n g e d f r o m l e f t t o r i g h t . T h e

s t a ti s ti c s a r e exp l a i ned i n Tab l e I fo r t he r e l a t i ve l y

s im p l e 8 p e r m u t a t i o n s o f th e t r i g r a m p a t t e r n s . I n a ll


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7 8

T A B L E I

Nuc leus reticularis thalami, neur on J1 (Files 228, 264); theoretical and empirical dis tribution of tr igrams; inverse deviations fr om ran-

dom mo del during bar pressing and subsequent gro omin g behav ior as mea sured b y sums of' in vers e ' chi-square values (Z ~). i .e. those that

resulted from emission and su ppression of the sam e pattern ()~ 2 and ;( ~, respectively) in two com pare d behavioral s tates

The list ing of 8 possible permutations of trigrams in the 1st column has be en arranged according to the binary numeric orde r where the

posit ion in the l ist is equal to the b inary num ber plus one, assum ing that signs (+ and -- ) are equivalent to (0) and (1), respectively.

The same principle w as used in l isting the hexagram patterns in the chi-square plots.

Bina ry represen- Pattern Theoretical Ba r pressing; M R = 43/s Gro om ing; M R = 40/s X

tation and se- prob ability Z 2 Z :

quential num ber Occurrence Occu rrence

Theoretical Observ ed Theoretical Obs erved

000 1 + + + 0.0 41 67 396 303 22s 532 698 52e 74

001 2 + + - - 0 .1 25 00 1188 997 31s 1596 1629 le 32

010 3 + - - + 0.2 08 33 1980 2560 170e 2661 2587 2s 172

011 4 + - - - - 0 .12 500 1188 923 59s 1596 1557 ls

100 5 - - + + 0.1 25 00 1188 1009 27s 1596 1628 le 28

101 6 - - + - - 0 .2083 3 1980 2483 128 e 2661 2516 8s 136

110 7 - - - - + 0 .12 500 1188 961 43s 1596 1557 ls

111 8 0.04167 396 269 41s 532 600 9e 50

Total 9504* 9505 540 1277 0* 12772 75 492

Con fidencelevel for df = 7 P < 0 .001 P < 0 .001

* T he small discrepancy between the theoretical and observed occurrences in this transcript from the co mp uter print-out was caused

by leaving out 5 digits after the decimal point in the theoretical values.

f i g u r e s , t h e c h i - s q u a r e v a l u e s t h a t r e s u l t e d f r o m a

m o r e f r e q u e n t o c c u r r e n c e a n d l e s s f r e q u e n t o c c u r -

r e n c e o f p a r ti c u l a r p a t t e r n s t h a n e x p e c t e d b y t h e r a n -

d o m m o d e l a r e r e p r e s e n t e d a s f il le d a n d o p e n c i r cl e

c o l u m n s , r e s p e c ti v e l y .

( 2) M i r r o r i n ve r se d e v ia t i o ns f r o m t h e r a n d o m m o d e l

M a n y p a t t e rn s e m i t t e d d u r i n g B P w e r e s u b se -

q u e n t l y s u p p r e s s e d b e l o w c h a n c e l e v el d u r i n g G R , S -

Q W a n d S W S . C o n v e r s e l y , p a t t e r n s i n i ti a ll y s u p -

p r e s s e d d u r i n g B P e p i s o d e s , w e r e s u b s e q u e n t l y

e m i t t e d d u ri n g S - Q W , G R a n d S W S . T h e s u m t o t a l

o f t h e s e p a ir e d i n v e r s e c h i - s q u a r e v a l u e s ( Z~ )

s e r v e d a s a n i n d e x o f th e i n v e r s e r e l a t i o n s h i p s ( e . g . i n

T a b l e I r i g h t ).

T h e s q u a r e - r o o t s o f t h e i n d i v id u a l c h i - s q u a r e v a l -

u e s (e a c h w i th d f = 1 ) c a n b e t r e a t e d a s n o r m a l d e -

v i a t e s 2. T h u s , t h e y w e r e u s e d t o c a l c u l a t e t h e

p r o d u c t - m o m e n t c o r r el a ti o n c o e ff ic i en t s f o r th e

e m i s s i o n m a g n i t u d e s o f p a t t e r n s d u r i n g B P a n d t h e

s u b s e q u e n t s u p p r e s s i o n s o f t h e s a m e p a t t e r n s d u r i n g

G R , S - Q W a n d SW S .

T o a s c e r ta i n t h e s i g n i f ic a n c e o f t h e t r e n d t o w a r d

c o r r e l a t i o n in th e w h o l e p o p u l a t i o n o f n e u r o n s , t h e

i n d i v id u a l n e u r o n a l c o r r e l a t i o n c o e f f i c i en t s w e r e

s u b j e c t e d t o t h e F i s h e r s z t r a n s f o r m a t i o n 39, a n d a

w e i g h t e d c o e f f i c i e n t w a s c a l c u l a t e d s e p a r a t e l y f o r

t h e B P e m i s s i o n s i n v e r s i n g t o ( S - Q W ; S W S ) s u p p r e s -

s io n s , a n d f o r t h e B P s u p p r e s s i o n s i n v e rs i n g t o ( S -

Q W ; S W S ) e m i s si o n s (F i g . 5 ) .

( 3) C o n v e n t i o n a l a n a l y s is o f s p i k e t r a i n s

A l l s p i k e t ra i n s w e r e a l so s u b j e c t e d t o t h e s t a n d a r d

n o n - s e q u e n t i a l s p i k e i n t e r v a l h i s t o g r a m a n a l y s i s

w h i c h y i e l d e d th e m e a n i n t e r v a l, m e a n r a t e, a n d t h e

s t a n d a r d d e v i a t i o n . T h e m e a n b u r s t d u r a t i o n ( B D )

a n d t h e i n t r a b u r s t r a t e ( i B R ) w e r e a l s o c a l c u la t e d

( T a b l e I I ) .

S e v e r a l s p ik e t r a i n s a m p l e s w e r e a n a l y z e d f o r a u -

t o c o r re l a ti o n 3 1 . I n t h e s e t e s t s t h e o r i g i n a l a u t o c o r r e -

l o g r a m s w e r e s u b t r a c t e d f r o m t h e a u t o c o n v o l u t i o n

h i s t o g r am s w h i c h s e r v e d a s c o n t r o ls f o r t h e o r d e r i n -

d e p e n d e n c e a m o n g i n t er v a l s o f a g i v e n s a m p l e 21.

T h e s e t e s t s , h o w e v e r , d i d n o t c o n t r i b u t e t o t h e d i f f e r -

e n t i a t i o n o f t h e b e h a v i o r a l s t a t e s , a n d w i ll n o t b e p r e -

s e n t e d h e r e .

RE SUL T S

E a c h o f 3 2 n e u r o n s w h o s e p l a c e m e n t s a r e m a r k e d

i n F ig . 1 y i e l d e d a t le a s t 2 1 0 0 s p i k e i n t e r v a l s f o r 5 o f

t h e b e h a v i o r a l s t a t e s : b a r p r e s s i n g p e r f o r m a n c e


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79

(BP), synchroni zed quiet wakefulness (S-QW),

SWS-1, SWS-2 and D -QW . In this neur onal pool, 6

neuro ns were also successfully moni tore d durin g the

episodes of grooming (GR) behavior.

The neurons have been classified into 3 types,

according to the criteria listed in Tabl e II: a group of

14 cells that can best be labeled as 'sleep onset ' ne u-

rons; because they showed highest patterning during

sleep onset; a group of 12 'mot or out put' n euron s be-

cause they showed highest patte rning during BP epi-

sodes; an d 6 ' indi fferent neu ron s', because their fir-

ing patterns remained relatively stable regardless of

the a nimal's behavioral state.

TABLE II

S W S o n s e t n e u r o n s ( i t i s n o t i m p l i e d t h a t t h e y a r e i n -

d u c t o rs o f S W S )

eneral characteristics

Three main features character ized th is cel l group

Table I I ) : a) the h ighest pat tern d evia t ion from the

r andom mod e l du r ing SWS-1 , a s mea su red b y the

sum to t a l o f t he Z2 values for 20 SWS-1 episodes ; b)

the emission of pat terns in the form of h igh f requ ency

and long up to 1 s) bursts dur ing 6--14 Hz E E G spin-

dles and/or del ta waves Fig. 2 and Fig . 3 r ight ); and

c) phasic uncoupl ing f rom the on-going SW S-2 proc-

ess and lapsing into 1--4 min lasting lulls of burstles s

General attr ibutes o f the nucleus reticularis ne urons divided into 3 types

Mean firing rate (MR), mean intraburst firing rate (iBR) per second, mean burst duration (BD), and chi-square values for deviations

from the random model of the hexagram pattern disbribution in spike trains recorded during the animal's bar pressing performance

(BP), grooming (GR), synchronized quiet wakefulness (S-QW), SWS-1, SWS-2, and desynchronized quiet wakefulness (D-QW)

C e ll t y p e B e h a v io ra l T o ta l n u m b e r o f M R iB R d B D d (m s )

state a patterns analy zed b

Dev ia t ion o f pa t te rn d istr ibu tion fro m

r a n d o m m o d e l

Z 2 (dr= 1260) c P critical Z 2

'Sleep onset' BP 145,650 28 198 110 3180 0.001 1417

(n = 14) GR 68,369 32 105 230 1740 0.001

S-QW 99,656 39 153 236 3802 0.001

SWS-1 122,345 49 206 560 6022 0.001

SWS-2 145,343 22 206 115 1233 0.9 1266

D-QW 80,660 20 208 72 1668 0.001 1417

'Motoroutput'BP 110,532 49 206 212 9340 0.001 1417

(n = 12) GR 83,442 41 149 515 4624 0.001

S-QW 87,562 45 160 102 2340 0.001

SWS-1 115,430 44 163 255 2443 0.001

SWS-2 123,667 24 176 145 1402 0.01 1379

D-QW 63,459 40 268 65 1706 0.001 1417

'Indifferent' BP 105,008 33 160 166 2133 0.001

(n = 6) GR 60,554 48 169 178 1995 0.001

S-QW 80,456 45 182 159 1867 0.001

SWS-1 98,451 44 156 188 1880 0.001

SWS-2 115,987 43 161 142 1967 0.001

D-QW 77,874 40 168 178 1723 0.001

1417

Each record was divided into 3 comparable in size samples from which a total of 20 were randomly selected for each state. The equal

number of samples across behavioral states facilitates comparison of the sums of chi-square values having the same degrees of free-

dom (df).

b The number of hexagram patterns 'extracted' from the spike trains is approximately 0.5-2 smaller than the number of interspike in-

tervals, hfter rejecting intervals greater than 800 ms and those that were 'equal' in sequential inequality tests based on resolution of

0.1 ms.

Degrees of freedom, df = (k-1)n, where k = 64, i.e. the number of hexagram categories or permutations whose occurrences were

tested against the theoretical values based on the random model; n = 20, i.e. the number of samples for each behavioral state. Thus,

the listed chi-square values can be defined by the formula:

1

a The burst was defined as a spike train whose initial 5 spikes occurred in less than 50 ms, and which were preceded and followed by an

interval greater than 100 ms.


6/16


7/16

8

I NR NEURON JA m' ,,,

I0 i 243/242 /0 0.

lo.'C _ B P

'l i i ~ iBR:105 N:18, 540; MR=20; "~ :1 60 i"

5~ 0

8 8~

o~

o

II I1

o~88

' , ~ o o i . o . , , . . ~ . . . . , ~ . . . . . . . , i , l l ~ < , , a

0 ~ 0 0 O(OX:X 3 0 0(0: , 0 0000 00

0: o . . o ;q : i ; i . : . . .1t I1 t

F - - + - - - - t 0 - - - - 4 - - - ' ~ + 0 - - - 4 - - - ~ + 0 - - - - 4 - - - 4 - - - - * - - - - 5 0 - - - + - - - 6 ~ - - - - , , , . , . ,

I0 ,,

S - Q W

I

o

ii |

N:5,800;

MR-19; "X~:1701"

5 ~ I o I iBR:IIO ~ -X2 /,,,~x:196;np=41

, , i i 8 i ~8 :8 o o ,..

O O

0:oo . . o | 0 8o oto i4. .8 .< ~i I ,~ . . ,~ , ~ , L ..... i ' l i i ~ i t l i l i

~ , - - - 4 . . . . 4. . . . 4. . . . 4 . . . 4, . . . 4- . . . ~ . . . . 4, . . . .~ . . . 4. . . . 4. . . . 4, . . . .

I I 0 20 30 40 50 60

Ill ;r tm

l 34 SWat- 1 N:30 00(1 ); MR:48; ~g~:186t

""

l O ~ h :

o i +BR=160 ,.,, .,l i .XE + ( BP )"281@; np=4 4

I

I~ 8 ~ *

0 i i l I . .i . h i l hL i_ i l J i i i l i ~

: 5 1 , ~ w , , , o ~ o , -

o"

< .

: : .

8 H i

.OJ le

- +---+ .... + .... 4. ... + .... + .... + .... 4. .... + .... 4. ... + .... 4. ... + ....

w m w m w W

J= I 10 20 30 40 50 60

O S W S - 2 N : 9 , 0 00 ; M R : 1 8 ; ~ : 3 9 ; P > .9 0

5 1 i iB R:I 30

e

0 J . . : ~ . : ~ , .~ = : : : : : % o o , ~ : : : : : : ~ k : : : _ : : : ~

P | I

' - - - - - - ' - - - - ' - - ' - '- - - - - ' - - - ' - - - - '- - - - - - - ' - - - ' . . . .

, : 6 ~ . 8 1 , ; , ~ : 3 1 ; ~ C : 3 s 8 +

11

30

i

i i {1

i

, w s

5 i

i

i i i

i ,

e e e e e

5~ . . . 0 00 08 o ~ 0~ 0

.

$ i

=~ .o ~ ~. ~ 8 N m

0 J oo oo olo o i e o oo ~ ( X l x ~ _ ~ _ _ _ C : ~ _ _ 9 _ _ _

O O O O H O O O O O O O O 4 N M k D O O O O O O ~ O OO

, - - - + . . . . , . . . . 4. . . . 4" . . . + . . . + . . . + . . . 4- . . . + . . . ~. . . . 4. . . . 4. . . . 100 # ' '1

Pattern =# 1 10 20 30 40 50 60 t df =6 3; Pz.O01 l''isec

+- +- +- +- +- - - +- +- +- - - - - 4.- - - - - - - - - - 4- - -- - 4. -- 4-- - 4. - -4'- - - -4. - - 4. - - - - - -~- -4 - - 4 -- +- - -

l . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

+ ++ 4 4 + + 4 4- 4 +4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

*++ + ++++ ++++ 4"4,++ +++4" 4"4"+4" 4"4"++ +4 "+ 4- BPe'~SWSs r 1 5 : . 7 8 ; P< O0 1

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

+++++ ++ +++ +++ ++ +++4-++4-4- 4"4"4"+4"4"+4" BPs--~SWSe r3 2 : . 2 4 ; P > 2

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

+ + ++ ++ + ++ ++ + 4 4 4 4 4. 4.'164

+ + + ++ + ++ + + + + 4 ,+ + 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

P a t t e r n s

Fig . 3 . Lef t : ch i -square p lo ts for devia t ions of pa t te rn occu rrences f rom the ra ndo m m odel in sp ike t ra ins emit ted by a ' s leep o nse t '

neuro n JA du ring BP, S -QW, SWS-1, SWS-2 and a long SWS episode , comprising several SWS-1 and SWS-2 episodes and last ing ap-

.proximate ly 40 min . The chi-square va lues (ordina te ) were p lo t ted by the comp uter for each of 64 possib le hexagram pa t te rns show n

at the bot tom (absc issa ) . The pa t te rns comp osed of 6 signs, are pr in ted ver t ical ly , and each should be ' read ' f rom the bot to m to the top

sign . The p a t te rns a re a rrange d according to the b inary pr inc ip le expla ined in Table I le ft , and a re num bere d from le f t to r ight . In the

chi-square p lo ts , the n umb ers an d a rrows indica te the ac tua l chi -square va lues of columns tha t were t ru nca ted to save space . Dur ing

BP, pa t te rns 22 and 43 were emit te d mu ch more of ten than predic ted by the ran dom model ( f i l led c i rcle columns) , whi le many other

pa t te rns occurred less of ten th an expec ted (open c i rc le columns) . The sum of the indiv idua l chi -square va lues showed a s ignificant de-

v i a ti on o f pa t te rn d i s t r i bu t ion f rom the r a n dom mode l (Z2 = 160, df = 63; P < 0 .001). D uring S-QW , severa l pa t te rns tha t were pre -

v iously emit ted dur ing BP became suppressed , and v ice versa , pa t te rns tha t were suppressed during BP became dominant dur ing S-

QW. The sum of 41 ' inverse ' ch i -square va lues (Zi ) equa led 196. During SWS-1, the inverse re la t ionships to the BP plo t becam e

even more apparent . Howev er , dur ing a short ep isode of SWS-2, the f i r ing pa t te rns fo l lowed the theore t ica l model . D uring a long epi-

sode of SWS, the inverse re la t ionships to the B P plo t were ap parent : a to ta l of 42 pa t te rns changed the i r d i rec t ion of devia t ion f rom the

rando m model , and the i r sum equa led 411. Right : the E EG excerpts a re shown toge ther wi th the ink records of uni t bursts ; the empty

and f il led t r iangles be low the top EE G t rac ing mark the non-rew arded an d rewarded ba r press respec t ive ly . Other abb revia t ions: N =

numb e r o f he xa g ra m pa t t e rn s a na lyz e d ; MR = me a n f i ri ng r a t e pe r se c ond ; iBR = me a n in t r a bu rs t fi r ing r a t e pe r se c ond .


8/16

82

t i m i n g w a s n o t e v e r c o n s i s t e n t , a n d t h e p a t t e r n s

c o u l d n o t b e l i n k e d t o a n y s p e c i f i c mo v e m e n t , i . e . a c -

t i v a t i o n o f a p a r t i c u l a r mu s c l e g r o u p . I n s o me i n -

s t a n c e s, s im i l a r d o u b l e t s w e r e e m i t t e d d u r i n g m o -

t i o nl e s s b u t a r o u s e d s t a t e ( D - Q W ) w h e n t h e a n i m a l s

a t t e n t i o n w a s f o c u s e d , e . g . o n m a n i p u l a n d a o r o t h e r

o b j e c t s .

attern analysis

Fi g . 3 s h o w s a n e x a m p l e o f t h e p a t t e r n a n a l y s i s o f

o n e o f t h e s l e e p o n s e t n e u r o n s , J A , i n t h e f o r m o f

c h i - s q u a r e p l o t s ( o r d i n a t e ) f o r 6 4 t e mp o r a l p a t t e r n s ,

e a c h s y mb o l i z e d a s t h e v e r t i c a l l y p r i n t e d 6 i n e q u a l i t y

s i g n s ( h e x a g r a m) a t t h e b o t t o m p l o t ; t h e p a t t e r n s o n

t h e a b s c i s s a a r e n u mb e r e d f r o m l e f t to r ig h t . A s

15 ~- NR NEURON A

I

' FILES 1 45/7 |

I

, BPa

I

' iBR=95 N=12,01 0; MR=22

5

o |~ I; ~C:123~ dr:63

L o

P ~

O - ~ . . _ : . . ; . . S . . , . . , . . . . . . . . . . . . . . ~ . . . k2 I

Pattern# 1

0 ] X ~ ~ t


9/16

83

p o i n t e d o u t b y t h e a r r o w , e a c h p a t t e r n s h o u l d b e

r e a d f r o m t h e b o t t o m t o t h e t o p si g n . S t r o n g p a t -

t e r n i n g c h a r a c t e r i z e d t h e B P e p i s o d e ; t h e m a i n c o n -

t r ib u t o r s t o th e d e v i a ti o n f r o m t h e r a n d o m m o d e l

w e r e t h e e m i t t e d p a t t e r n s 2 2 a n d 4 3 ( f i l l e d c i r c l e c o l -

u m n s ) , g e n e r a t e d b y b u r s t s o f d o u b l e s p i k es . I n a d -

d i t i o n , m a n y p a t t e r n s t h a t w e r e e x p e c t e d t o o c c u r a t

= : B P e n : 1 5 ( O W ; S W S ) s r = . 8 8 P < . 0 0 1

n= 33

o - o B P s = ( Q W ; S W S ) e r = . 4 9 P < . 0 5

4

3

2

1

I I I

o

/ e /

o / /

o

o oo / / '

/

o o ~ , . ~ % ~

0 0 o S ~

/ /

, 2 / .

1 o

a D ~ o

S~ ~ o Neuron JA

/ / < 3 3

/ ~o CP files 1 62 /2 42

243

l e a s t a t t h e c h a n c e l e v e l w e r e s t r o n g l y s u p p r e s s e d

( o p e n c i r cl e c o l u m n s ) , a p p a r e n t l y o w i n g t o c o n -

s t ra i n ts t h a t m o d u l a t e d t h is n e u r o n s a c t iv i t y d u r i n g

B P . T h e s u b s e q u e n t S - Q W e p i s o d e a ls o s h o w e d

s t r o n g p a t t e r n i n g b u t o f a d i f fe r e n t c h a r a c t e r , a l-

t h o u g h t h e m e a n f ir in g ra t e ( M R ) w a s c o m p a r a b l e t o

t h a t o f t h e B P e p i s o d e . A p p a r e n t l y , t h e l o n g fi ri n g

n -15 e - -e

B P e : ~ - ~ ( Q W ; S W S ) s r = . 8 5 P < . 0 0 1

n= 36 o,-,o

B P s- -- -- ~ ( OW ; S W S ) e r : . 32 P < . 0 5

U)

2

0 S S ~

S J ' S X

0 S S

%o o~

~e.s~

; j

~ Qs

~ y : .oo

oOm- ~ 0 Ne uro n A

~ 1 4 5 1 7 3 0 0 1 2

2 2

10, i

o l i a i i i

I L

o o

n = 8

8 - e - - e B P e - - -~ G R ; Q W ; S W S ) s r = .7 6 P ~ .0 3

tn o o o o B P s n ~ G R ; Q W ; S W S ) e r = -. 37 P -~ .0 3

~ 6 - o 8 o

.

I

4 - o.o', o

2 - .. . ~ o 8 ~ o s ~

o o o ~ o 0 J1 fi les

2 2 8 1 2 6 4 1 2 6 8 1 2 6 6

I I l I I

I l

2 4 6 8 10 1 2 14 1 6 1 8 20

Fig. 5. Thr ee representative examples o f correlation between the emission magnitudes of pattern during BP and their subsequent defi-

cits, i .e. suppressions during the com bined Q W an d SW S episodes (top two plots; BPe---*(QW, SW S)s) or combined G R , Q W and

SWS episodes ( the bo t tom plot ; B Pe-- , (G R, Q W , SW S)s; f il led c irc le va lues). T he devia tion m agnitudes f rom the random model

were measured in ~ values as indicated on the ordinate an d abscissa. In addition, each plot shows the correlation between the sup-

pression magnitudes of patterns d uring BP and their subsequent em issions during the combined QW and SW S or during GR , Q W and

SWS (ope n circle values). The values of n abov e each transition arrow are equal to the num ber of patterns involved. The to p two plots

represent the sleep onse t neuro ns JA and A w hose firing patterns were analyzed in Figs. 3 and 4, respectively; the bottom plot exem-

plifies the behavior of a m oto r ou tpu t neu ron whose pattern distribution w as analyzed in Fig. 7.


10/16

I

b u r s t s ( s h o w n o n t h e r i g h t o f F i g. 3 as p o l y g r a p h i c

t r a c in g s t o g e t h e r w i t h th e E E G ) c o n t a i n e d m o s t l y

t h e ' a c c e l e r a n d o ' t y p e p a t t e r n s , s y m b o l i z e d a t t h e

b o t t o m c h i - s q u a r e p l o t as th e p a t t e r n s d o m i n a t e d b y

- - s ig n s. S e v e ra l m o r e c o m p l e x p a t t e r n s , c o m p o s e d

o f s i gn s + a n d - - a l s o c o n t r i b u t e d t o t h e t o t a l d e v i a -

NR NEURON J1; FILES 228/264

10~ D-QW ~ D-Q W immediately af te r BP

, N=1000; MR=34;~X~=32; df=31; : N=1000; MR=20; P


11/16


12/16

86

c o r t e x a x o n s a n d t h e N R c e l l s . I n t h e p r e s e n t s t u d y ,

t h e p o s s i b i l i t y c a n n o t b e e x c l u d e d t h a t t h e N R n e u -

r o n s f i r e d i n r e s p o n s e t o t h e p r o p r i o c e p t i v e i n p u t o r

t o t h e e x c i t a t o r y i n p u t f r o m t h e f r o n t o - o r b i t a l c o r t e x

w h i c h i s li k e l y t o p l a y a r o l e i n t h e a t t e n t i o n p r o c e s s -

C S 3 4 .

attern analysis

T h e s e l e c t i v e a n d s t r o n g e m i s s i o n o f t r a i n s o f

' d o u b l e t s ' , r e s u l t e d i n e x t r e m e l y h i g h c h i - s q u a r e v a l -

u e s f o r p a t t e r n s c o n s i s t i n g o f t h e a l t e r n a t i n g s i g n s +

a n d - - , i n t h e b a c k g r o u n d o f c h i - s q u a r e v a l u es f o r a b -

s e n t o r s u p p r e s s e d p a t t e r n s ( o p e n c i r c l e c o l u m n s ) ,

e .g . in F igs . 6 and 7 .

T h e h e t e r o g e n o u s n a t u r e o f t h e s y n a p t i c d r i v e r e -

c e i v e d b y t h e ' m o t o r o u t p u t c e l l s' w a s i n d i c a t e d b y

t h e i r a c t i v a t i o n d u r i n g t h e a n i m a l ' s g r o o m i n g b e h a v -

i o r ( G R ) , w h e n t h e E E G o v e r t he p a r i e t o -o c c i p i t a l

c o r t e x showe d 7 - 10 Hz sp ind le s ( e . g . i n F ig . 6 r i gh t ) .

T h e G R s p i k e t r a i n s w e r e d e v o i d o f ' d o u b l e t s ' , a n d

,EUR0, J1 ~ILE.+ 22 8 , 266

ZO F i I , 2O4, 2O8

i 411 I I

II , i A

,,

10

i

+=+++; d,+:++

: : | o o o , , P


13/16

87

i n s te a d c o n s i s t e d o f t h e l o n g ' r i t a r d a n d o - a c c e l e r a n -

do ' s p i ke t r a i n s (F i g . 6 r i gh t ) t ha t r e s u l t ed i n h i gh ch i -

s q u a r e v a l u es f o r p a t te r n s c o m p o s e d o f s e q u e n c e s o f

s igns - - and + i n F i g s . 6 and 7 . In th i s and o t he r neu -

r o n s , t h e m o s t i n t r ig u i n g a s p e c t o f t h e c h i - s q u a r e

p l o t s f o r G R b e h a v i o r w a s t h a t t h e i r p r o f i l e s w e r e

v i r tu a l l y id e n t i c a l t o t h o s e o f S W S o f t h e ' s l e e p o n s e t '

ce l l g rou p ( c om par e F i g . 7 w i t h F i g s. 3 and 4 ) .

F i g . 6 i l l u s t r a t e s t h e r e m a r k a b l e c o n s i s t e n c y a n d

s e l e c ti v i ty o f p a t t e r n s e m i t t e d b y n e u r o n J1 d u r i n g

t w o B P a n d t w o G R e p i s o de s t a k e n f r o m m u c h l on g -

e r r e c o r d s . F o r t h e s a k e o f b r e v i t y , t h e a n a l y s is i s

b a s e d o n t h e d i s t r i b u t i o n o f 3 2 p e n t a g r a m p a t t e r n s .

B y c o m p a r i n g th e t o p B P a n d G R p l o ts , o n e c a n f in d

a t o t a l o f 2 4 p a i r s o f ' i n v e r s e ' c h i - s q u a r e v a l u e s f o r

c o r r e s p o n d i n g p a t t e r n s , a n d t h e i r s u m ( X 2 = 2 8 3 ).

T h e s u m o f t h e ' i n v e r s e ' c h i - s q u a r e v a l u e s f o r t h e b o t -

t o m B P a n d G R p l o t s w a s e v e n g r e a t e r ( X 2 = 5 4 1 ) .

I n o r d e r t o a l l e v i a t e d o u b t s t h a t t h i s c o n s i s t e n c y o f

p a t t e r n s s h o w n i n F i g . 6 m i g h t n o t b e p h y s i o l o g i c a l

a n d c a u s e d b y n e u r o n a l i n j u r y , s h o r t e p i s o d e s o f D -

Q W a r e in c l u d e d th a t i m m e d i a t e l y p r e c e d e d t h e B P

p e r f o r m a n c e a n d t h e G R b e h a vi o r. * F i g. 7 is a n e x -

t e n s i o n o f F i g . 6 a n d i s b a s e d o n m u c h l o n g e r e p i -

s o d e s o f B P a n d G R f r o m n e u r o n J l. T o f a c i l it a te

c o m p a r i s o n o f t h e p l o t s , t h e B P e p i s o d e w a s p l a c e d

b e t w e e n t h o s e o f G R a n d S - Q W , a l t h o u g h t h e r e-

c o r d i n g s e q u e n c e w a s B P , G R , S - Q W a n d S W S . P lo t -

t i n g t h e B P p a t t e r n e m i s s i o n m a g n i t u d e s a g a i n s t t h e

c o r r e s p o n d i n g s u p p r e s s i o n s in t h e c o m b i n e d G R , S -

O W , a n d S W S s a m p l e s , y i e l d e d a s i g n if i c a n t c o r r e l a -

t i on coe f f i c i en t ( r 8 = +0 .76 ; P - 0 . 03 ; F i g . 5 bo t -

t o m , f i ll e d c ir c le v a l u e s ). C o n v e r s e l y , p l o t t i n g t h e B P

s u p p r e s s i o n s c h a n g i n g t o e m i s s i o n s i n t h e c o m b i n e d

G R , S - Q W a n d S W S e p i s o d e s , y i e l d e d a s i g n i f i c a n t

n e g a t i v e c o r r e l a t i o n r 3 6 = ---0 .37; P --- 0.03 ;

C o rre la t io n coe f f ic ien t ; | /~ .Bp e

- I A . S . .Q W ;

SWS) s

- .4 - ,2

| | |

mt~ MO cells

eo SWSo ce l ls

0.0 + .2

.10 ns

+ .4 + .6 + .8

i I I I I I I

n = 12 1 .68 p


14/16

88

F i g. 5 b o t t o m , o p e n c i r c l e v a l u e s ) . T h i s d i v e r g e n c e i n

t h e s l o p e o f c o r r e l a t i o n , d e p e n d i n g u p o n t h e d i r e c -

t i o n o f p a t t e r n i n v e r s i o n s , w a s c h a r a c t e r i s t ic o f t h e

' m o t o r o u t p u t n e u r o n s ' , a n d c o n t r a s t e d w it h th e

m o r e u n i f o r m b e h a v i o r o f t he ' sl e e p o n s e t n e u r o n s '

(F i g . 8 ) . Acros s t he who l e ce ll g ro up (n = 12 ) , t he

w e i g h t e d c o r r e l a t i o n c o e f f i c i e n t f o r B P e r e v e r s i n g t o

(S -Q W , S W S )s was s i gn i f ican t ( r w = +0 .68 ; P 0 . 4 ) .

I n d i f f e re n t n e u ro n s

As s how n i n F i g . 1 ( s t a r s ) , t he d i s t r i bu t i on o f t hes e

c e l ls w a s n o t r e s t r i c t e d t o a n y p a r t o f th e N R . A c r o s s

a ll b e h a v i o r a l s t a te s , t h e m e a n f i ri n g r a t e s a n d t h e

m e a n i n t r a b u r s t r a t e s ( T a b l e I I ) r e m a i n e d r e l a t i v e l y

u n c h a n g e d c o m p a r e d t o o t h e r t w o c e l l g r o u p s . T h i s

' r i g i d i t y ' was a l s o r e f l ec t ed i n cons i s t ency o f t he ch i -

s q u a r e v a l u e s f o r p a t t e r n d e v i a t io n s f r o m t h e r a n d o m

m o d e l ( T a b l e I I r i g h t) . T h e c h i - s q u a r e p l o t s ( n o t

s h o w n ) w e r e d o m i n a t e d b y p a t t e r n s c o m p o s e d o f a lt -

e r n a t i n g sig ns ( + a n d - - ) g e n e r a t e d b y s h o r t

(100 -200 m s ) bu r s t s o f s p ikes . O n l y i n t wo i n s t ance s ,

t h e s e n e u r o n s c o u l d b e i n d u c e d t o a l t e r t e m p o r a r i l y

t h e i r f ir i ng p a t t e r n s w h e n a n e m o t i o n a l l y s t r o n g s ti m -

u l u s was p re s en t ed t o t he an i m a l s , s uch as a l ive r a t in

a p l ex i g l as box ( t he ch i - s quare p l o t s no t s hown) .

T h e s e p a t t e r n c h a n g e s w e r e n o t o f th e m i r r o r i n v e r-

s i on t y p e d e s c r i b e d f o r t h e o t h e r t w o c e l l g r o u p s .

DISCUSSION

Genesis o f pa t tern invers ions

I n a d d i t i o n t o t h e e v i d e n c e a l r e a d y d i s c u s s e d i n th e

I n t r o d u c t i o n , o t h e r o b s e r v a t i o n s , i n c l u d i n g t h e r e -

s u lt s o f th e p r e s e n t s t u d y , l e n d s u p p o r t t o o u r c o n t e n -

t i o n t h a t t h e f i r in g p a t t e r n s , a n d t h e i n v e r s i o n s o f

t he i r s t a t i s t i ca l d i s t r i bu t i on r e f l ec t and a re caus ed by

c h a n g e s i n r e c e p t o r s a t t h e s o m a - d e n d r i t i c s i t e s o f

N R n e u r o n s .

First,

r e c e p t o r d e s e n s i t i z a t i o n i s k n o w n t o b e a f -

f e c t e d i n v i t r o b y a g o n i s t c o n c e n t r a t i o n , e x p o s u r e

t i m e , a n d m e t a b o l i c a l t e r a t i o n s 3s, a n d i n v i v o b y t h e

f r e q u e n c y o f i m p u l s e s t h a t r e l e a s e t h e t ra n s m it te r S 0.

T h e r e f o r e , d e s e n s i t i z a t i o n i s a g r a d e d p r o c e s s .

H e n c e , i t o f f e r s a p l a u s i b l e e x p l a n a t i o n o f t h e p o s i -

t i v e c o r r e l a t i o n b e t w e e n t h e e m i s s i o n m a g n i t u d e s o f

p a t t e r n s a n d t h e i r s u b s e q u e n t d e f i c i t s , o n c e t h e p u r -

p o s i v e b e h a v i o r i s te r m i n a t e d .

S e c o n d , i n b e h a v i n g c a ts n o t o n l y d i d t h e N R n e u -

r o n s s h o w t h e p a t t e r n i n v e r s i o n s , b u t a ls o n e u r o n s i n

t h e n u c l e u s c e n t r u m m e d i a n u m 24, p a r t i c u l a r ly a f t e r

m o r p h i n e s u l fa t e ( 1 m g / k g , i . m , ) 6. M o r e o v e r , t h e

m o r p h i n e - i n d u c e d i n v e r s i o n s c o u l d b e a b o l i s h e d a n d

t h e p r e - d r u g p a t t e r n s c o u l d b e p r o m p t l y r e s t o r e d b y

t h e m o r p h i n e a n t a g o n i s t , n a l o x o n e 6.

Third , t h e n u m b e r s o f c h o l in e r g i c , a - a d r e n e r g i c ,

b e n z o d i a z e p i n e , a n d o p i a t e r e c e p t o r s in t h e r a t b r a in

f a ll 3 0 - 7 7 d u r i n g t h e a n i m a l ' s e x p l o r a t o r y b e h a v -

ior , a nd r i se du r ing the res t a nd s leep pe r iod ~8,19. T he

g r a d u a l d e c l i n e in t h e n u m b e r s o f t h e c h o l i n e r g ic a n d

a - a d r e n e r g i c r e c e p t o r s m a y b e a s t r o n g e n o u g h f a c -

t o r l e a d i n g t o i n v e r s io n o f t h e N R f i ri n g p a t t e r n s a n d

i n d u c t io n o f S W S , b e c a u s e t h e s e s y s t e m s a r e k n o w n

t o c o n t r o l t h e t h a l a m o - c o r t i c a l t r a n s a c t i o n s d u r i n g

wa kefu lness and pu rpo s ive behavior19,25.401

I m p l ic a t io n s f o r t he f u n c t i o n o f S W S

T h e l o g ic a l q u e s t io n i s w h e t h e r t h e r e i s a r e a s o n t o

b e l i e v e t h a t t h e u n a b a t e d ( o r m a r k e d l y e n h a n c e d )

t hough ' i nve r s e ' d i s t r i bu t i on o f f i r ing pa t t e rn s i n t he

N R a n d o t h e r t h a l a m i c n u c l e i m a y h a v e a r e c u p e r a -

t i ve ro l e . In v i t ro s t ud i es s howed t ha t , upon a s i m p l e

r e m o v a l o f a r e c e p t o r a g o n i s t , t h e r e s e n s i t i z a t i o n o f

b r a in f l - a d r e n e r g i c r e c e p t o r s is a s l o w p r o c e s s , w h i c h ,

h o w e v e r , c a n b e m a r k e d l y e n h a n c e d b y a b r i e f p o t a s-

s i u m - i n d u c e d d e p o l a r i z a t i o n 38. T h e e n h a n c e m e n t o f

r e s e n s i ti z a t io n a p p e a r s t o b e m e d i a t e d b y t h e m e m -

b r a n e d e p o l a r i z a t i o n a l o n e r a t h e r t h a n t h e c o n c o m i -

t a n t r e l e a s e o f t r a n s m i t t e r s , b e c a u s e p r e v e n t i o n o f

t h e ir r e l e a se b y r e m o v i n g C a 2 + fr o m t h e m e d i u m

does no t i n t e r f e re wi t h r e s ens i t i za t i on , wh i l e t he t e -

t r o d o t o x in - i n d u c e d b l o c k o f N a + c o n d u c t a n c e

d o e s 38. M e m b r a n e d e p o l a r i z a t i o n a l so r e s e n s it i z es

t h e a c e t y l c h o l i n e a n d a - a d r e n e r g i c r e c e p t o r s i n t h e

p e r i p h e r a l o r g a n s ( c f . r e f . 3 8 ) . C o n s i d e r i n g t h e

m e c h a n i s m s o f p a t t e r n g e n e r a t i o n ( s e e I n t r o d u c -

t i on ) , t he i nve r s i ons o f t he s t a t is t i ca l d i s t r ibu t i on o f

f i r i ng pa t t e rn s a re l i ke l y t o r e s u l t f rom t he i nve r s i on

o f s pa t i a l d i s t r i bu t i on o f t he depo l a r i z i ng i m pu l s es a t

s om a-de nd r i t i c s it e s . Th us , t he d i s t r i bu t i on o f t he ac -

t i ve s i t e s du r i ng S W S s hou l d cons t i t u t e a nega t i ve

i m age o f s i t e s t ha t were ac t i ve du r i ng t he an i m a l ' s

p u r p o s i v e b e h a v i o r a s s h o w n i n t h e d i a g r a m o f F i g . 1

( b o t t o m ) . S u c h a n a r r a n g e m e n t m a y b e m o s t e f f e c -

t i ve i n t he p roces s o f r e s ens i t i za t i on i f t he phas i c


15/16

m e m b r a n e d e p o l a r i z a t i o n d o e s i n d e e d p l a y a s i gn i fi -

c a n t r o l e .

I m p l ic a t io n s f o r t h e ge n e si s o f S W S

T h e i n v e r s io n s o f p a t t e r n d i s t r i b u t i o n w a s c l e a rl y

e v i d e n t s h o r t l y a f t e r t h e a n i m a l s c e a s e d b a r p r e s s i n g ,

i .e . d u r in g S - Q W a n d e v e n g r o o m i n g b e h a v i o r w h i c h

i s r e g a r d e d a s a n i n s t i n c t i v e - li k e a c ti v i t y p r e p a r a t o r y

t o S W S c o m m o n t o fe l i n e s ( c f. re f . 2 9 ) . T h u s , t h e i n -

v e r s i o n p r o c e ss , p r e s u m a b l y c a u s e d b y r e c e p t o r

c h a n g e s , a p p e a r s to re p r e s e n t a g r o w i n g c o n t i n u u m

w h i c h m a y g e n e r a t e th e n e e d f o r s l e e p .

I n t h e b r a i n s t e m , o s c i l l a t o r y i n t e r a c t i o n h a s b e e n

d e s c r i b e d b e t w e e n t h e g i g a n t o c e l l u l a r ( c h o l i n e r g i c

a n d e x c i t a t o r y ) s y s t e m a n d t h e a m i n e r g i c ( i n h i b i t o r y )

n e u r o n s ( c f. r ef . 3 6 ). T h e i n v e r s e l y r e l a t e d f i r i n g

r a t e s in t h e s e s y s t e m s m a y a c c o u n t f o r p h a s i c o c c u r -

r e n c e o f ra p i d e y e m o v e m e n t s l e ep e p i s o d e s a n d

R E F E R E N C E S

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c idence de tec tor ? lsr. J. Med. Sci. 18 (1982) 83-92.

2 A r mi tage , P . , Statistical Methods in Medical Research J.

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3 Bar r ionuoevo, G . , Benoi t , O . and Tempie r , P . , Evidence

for two types of f i r ing p at terns dur ing s leep -waking cycle in

the ret icu lar thalam ic nucleus of the cat , Exp. Neurol. 72

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4 Ber gmann, B . , Rechtschaf f en , A . , W inte r , J . and G i l l i -

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5 Br udno, S . and Mar czynski , T . J . , Temp or a l pa t te r ns , the i r

d i s t r ibu t ion and r edund ancy in t r a ins of spontaneous neu-

r ona l sp ike in te r va l s o f the f e l ine h ippocam pus s tud ied w i th

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6 Burns , L. L. and M arczynski , T. J . , Pat terning of neuronal

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mor phine , Soc. Neurosci. Abstr. 5 (1979) 606.

7 Burns, L. L. an d M arczynski , T. J . , Phasic loss of con-

s traints in t iming of neuronal spikes in the fel ine centrum

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9 Carm an, J . B. , Cowan, W . M. and Powell , T. P . S . , Cor t i-

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10 Dun widdie, T . , N europh ysiological a l terat ions following

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11 Fe inber g , I. and Evar t s , E . V . , Changing concepts of the

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89

S W S . O u r o b s e r v a t i o n s o n t h e i n v e r s i o n s o f s t a ti s ti c -

a l d i s t r i b u t i o n o f f i ri n g p a t t e r n s ( i n d e p e n d e n t o f th e

m e a n f i ri n g r a t e s ) m a y r e f l e c t t h e p r e s e n c e o f a m o r e

i n f l u e n t ia l a n d y e t s u b t l e o s c i l l a t o r y s y s t e m b a s e d o n

r e c i p r o c a l c o n n e c t i v i t ie s b e t w e e n t h e N R a n d o t h e r

n e u r o n a l e n s e m b l e s . I t a p p e a r s th a t o n e p a t t e r n o f

s u c h c o n n e c t i v i ti e s s u p p o r t s w a k e f u l n e s s a n d g o a l - d i -

r e c t e d b e h a v i o r , w h i l e t h e o t h e r , w i t h d i f f e r e n t a n d

p r o b a b l y c o m p l e m e n t a r y s o m a - d e n d r i t i c d i s t r i b u t i o n

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