multi-site recordings in tg4510 mice
DESCRIPTION
Multi-site recordings in Tg4510 mice. Liam Scott. Hippocampus: Area. Area (mm2). 3m. 7m. 7 month male Tg4510 mice show decreased MWM performance and hippocampal cell loss. 3 vs. 7 month old Tg4510 male mice show:. (Wildtype for comparison). Data: Kawabe, Klein, Milici. - PowerPoint PPT PresentationTRANSCRIPT
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Multi-site recordings in Tg4510 mice
Liam Scott
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Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show decreased MWM performance and hippocampal cell loss
Are
a (
mm
2)
1
1.2
1.4
1.6
1.8
2
2.2
2.4
2.6
2.8
3 months 6 months 8 months 10 months
Wild Type
Bigenic 4510
40
50
60
70
80
90
100
110
% W
ild T
ype
3 M 6M 8 M 10 M
Wild Type
Bigenic 4510
Normalized Ca1 Thickness
Hippocampus: Area
1 2 3 40
500
1000
1500
M++M--
F++F--
Day of testing
Len
gth
of
Pat
h (
cm)
***
*
3m
1 2 3 40
500
1000
1500
** * ** *
**
Day of testing
7m
3 vs. 7 month old Tg4510 male mice show:
(Wildtype for comparison)
Data: Yabe, Moore, Roof Data: Kawabe, Klein, Milici
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1174 1176 1178 1180 1182 1184 1186 1188 1190 1192 1194 1196 1198 1200 1202 1204 1206 1208 1210 1212s
Keyboard311000
0
-1000
uV
CA
1 E
EG
1
5274 5276 5278 5280 5282 5284 5286 5288 5290 5292 5294 5296 5298 5300 5302 5304 5306 5308 5310 5312s
Keyboard311000
0
-1000
uVC
A1
EEG
1
Stimulation of the nPO drives the hippocampal EEG in anesthetized rats and mice
NPO
Hippo
EEG Stimulus
6-seconds
0.06 0.08 0.10 0.12 0.14 0.16
5.5
6.0
6.5
7.0
7.5
8.0
Fre
quen
cy (
Hz)
Stim Current (mA)
Theta Frequency
0.06 0.08 0.10 0.12 0.14 0.1615.0k20.0k
25.0k30.0k
35.0k40.0k
45.0k50.0k
Theta Power
The
ta P
ower
(V
2 )
Stim Current (mA)
0 5 10 15HzFrequency
10000
5000
0
uV^2
CA
1 E
EG
1
0 5 10 15HzFrequency
2000
1000
0
uV^2
CA
1 E
EG
1
–5-HT
–Hippocampal Formation
–pcells
–Median Raphe
–Gl
u
–ga
ba
–ACh
–Medial Septum
–Nucleus Pontis Oralis
–(nPO)
–Gl
u
–Supramammilary Bodies
–(SUM)
–Gl
u
–ga
ba
–ga
ba –ga
ba
–ga
ba
–5-HT
–Adapted from: RP Vertes (2005) Hippocampus 15:923-35
–= +–= -
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Determining electrode position using stimulation of nPO
4
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7 month male Tg4510 mice show decreased nPO-evoked hippocampal theta power and total power
Peak Frequency Relative Theta Power
Theta Power Total Power
** *
*
*
* * * *
***
**
*
*
**
* *
* *
**
(*=P<0.05, **=P<0.01, ***=P<0.001 ; unpaired t-test)
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Perforant path – dentate gyrus LTP
6
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Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Determining electrode position using stimulation of perforant path
7
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7 month male Tg4510 mice show reduced amplitude of perforant path-evoked dentate gyrus population spike
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Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show reduced amplitude of perforant path-evoked dentate gyrus population spike
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7 month male Tg4510 mice show no change in perforant path - dentate gyrus LTP
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–control
CA-1
DG
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CA-1
DG
DG population spike
CA1 population spike
–Tg
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Summary
Stimulated theta• No change in theta frequency or relative theta• Reduction in theta power and total power
PP-DG LTP• Reduction in amplitude of evoked population spike• No change in LTP due to HFS
All observations can be explained by reduction in cell number in hippocampal formation???
14
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