the neurobiology for a sense of direction
TRANSCRIPT
Neuro Biology for a Sense of Direction
Dr. Jeffrey Taube, Dartmouth 1
The Neurobiology for a Sense of Direction
Jeffrey Taube
Dartmouth College
Hanover, NH
OutlineNature of Head Direction Cell activitySensory PropertiesCircuitry - How and where is the signal generatedNavigationResponses in 3-D
Neural Substrates of Spatial Cognition
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Navigation and the Hippocampus
1. Behavioral studies with animalsMorris water taskRats with hippocampal lesions are impaired in finding the
platform.
2. fMRI and PET studies with humansLondon taxi cab driversActivation of right hippoampus when recalli ng routes
3. Physiological recordings from single neurons in thehippocampus of freely-moving animals - Place cells
Human Data
• Maguire et al. (1997), J Neurosci. 17: 7103-7110• Maguire et al. (1997), J Neurosci. 17: 7103-7110
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Two Components of Spatial Orientation
• Location - Place cells
• Directional heading
But place cells do not provide informationabout directional heading.
A second category of spatial cells encodes for directional heading - Head Direction cells
Head Direction Cell Video
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Head Direction Cell Properties
• Direction of head, not body position.
• Head direction in the horizontal plane.
• Fires whether animal is moving or still .
• Firing is independent of location and behavior.
• Each cell exhibits one preferred firing direction.
• Preferred firing directions distributed equally around 360º.
• Little adaptation in cell firing when the rat holds its head in the cell ’s preferred firing direction.
Head Direction Cell Tuning Curve
Firing Rate (Hz)
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Preferred firing direction
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90°
180°
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Background firing rate
Directionalfiring range
Head Direction (°)
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3 typical HD cells, each with a different peak fir ing rate
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Head Direction (°)
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Low Medium
High
What controls the preferred firing direction of HD cells ?
Experiment: Rotate the cue card.
Does the cue card exert stimulus control overhead-direction cell firing?
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180° Cue Card Rotation
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Standard 1
180° Card Rotation
Standard 2
Head Direction (degrees)
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Does removing the salient visual cue alter cell firing?
Experiment: Remove the cue card.
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Preferred Firing Direction is Maintained in the Absence of the Cue Card
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Cell 1-Standard SessionCell 2-Standard SessionCell 1-No Cue Card SessionCell 2-No Cue Card Session
Firing Rate (Hz)
Head Direction (°)
Does a change in the shape of the environment have an effect on cell firing?
Experiment: Place the animal in a rectangularor square enclosure with the cue card inthe same relative position.
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Rectangle & Square vs Cylinder
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Head Direction (°)
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How is the HD Cell Signal Generated?
M Witter (1989) In Hippocampus: New Vistas
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Circuit Diagram - 1Circuit Diagram - 1
PostsubiculumAnterior Dorsal Thalamus
Lateral Mammillary Nuclei
Lateral Dorsal Thalamus
Posterior Cingulate Cortex
Subiculum
Posterior Parietal Cortex
Hippocampus Entorhinal Cortex
Place Cells
HD Cells
3 Typical HD Cells
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Anterior Dorsal Thalamus
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16 Postsubiculum
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Lateral Mammillary NucleiFiring Rate (Hz)
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Postsubiculum Anterior Dorsal Thalamus
Lateral Mammillary Nuclei
Lateral Dorsal Thalamus
Posterior Cingulate Cortex
Subiculum
Posterior Parietal Cortex
Hippocampus Entorhinal Cortex
Place Cells
HD Cells
Where are HD cells located?
How is the HD Cell Signal Generated?
Given that the HD cells have been identified in several brain areas, which areas are critical for generating the signal?
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Lesions in any of several different nuclei do not abolishHD cell firing in the AD Thalamus, but lesions in the AD
Thalamus do abolish HD cell activity in the Postsubiculum.
Postsubiculum
Lateral Mammillary Nuclei
Lateral Dorsal Thalamus
Posterior Cingulate Cortex
Subiculum
Posterior Parietal Cortex
Hippocampus Entorhinal Cortex
Place Cells
HD Cells
Anterior Dorsal Thalamus
HD Cells Present
Lesions in the Lateral Mammillary Nuclei disrupt HD activity in the Anterior Dorsal Thalamus
Circuit 3- LesionsCircuit 3- Lesions
Postsubiculum
Lateral Mammillary Nuclei
Lateral Dorsal Thalamus
Posterior Cingulate Cortex
Subiculum
Posterior Parietal Cortex
Hippocampus Entorhinal Cortex
Place Cells
HD Cells
Anterior Dorsal Thalamus
No Cells
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Lesion Studies Conclusions
Lesions of the Lateral Mammillary Nuclei (LMN) led to the absence of finding HD cells in the Anterior Dorsal Thalamus.
The LMN and neural information projected to it are critical for the generation of HD cell activity.
So, what brain areas and what type of information is projected to the LMN?
Vestibular Apparatus
Saccule
Directionof view
Vestibular nerve
Facial nerve
Cochlear nerve
CochleaSpiral ganglionof cochlea
Utricle
Saccularnerve
Vestibularganglia ofScarpa
Superiorsaccularramus
Semicircularcanals: (ducts)
SuperiorPosteriorLateral
Endolymphatic sac
Otolith Organs
[from Kandel, Schwartz & Jessell, (1994), Principles of Neural Science, 3rd Ed.]
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Interaction of the Vestibular System• HD cell firing in the Anterior Dorsal Thalamus and in
the Lateral Mammillary Nuclei (but not in the Postsubiculum) is modulated by angular head velocity.
• Vestibular deficient humans - Mild navigational impairments due to enhanced reliance on visual cues. But more severe deficits are seen during navigation in the dark or when blindfolded.
• Following a head turn, perhaps a vestibular system signal is fed forward onto HD cells to update the new head direction?
Influence of Vestibular Lesions on Head Direction Cells
Protocol:
A. Isolate Head Direction cell .
B. Under anesthesia, inject intra-tympanic sodium arsanilate.
C. Following recovery after ~ 1 hr, monitor HD cell over the course of the vestibular lesion.
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Inhibition of contact-righting by foot contact in the labyrinthectomized rat.
Chen et al., 1986, Physiol Behav 37: 805-814.
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VestibularLesion: Intact
Neuronal Discharge
post 1 hr
pre
post 24 hr
post 96 hr
50µV
200 µsec
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Transient Vestibular Lesion using TTX
Pre Post 1 hr Post 12 hr Post 24 hr Post 48 hr
Firing Rate (Hz)
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Post 24hr
Post 48hr
Head Direction (°)
Vestibular inputs may also be important for establishing spatial representations for location.
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Transient Vestibular Inactivation Disrupts CA1 Place Cell Firing
TTX Recovery
Pre Post 1hr 4hr 12 hr 24 hr 36 hr 48 hr
If the HD cell signal generation is dependent upon vestibular input, then …
How is a vestibular signal conveyed to theHD cell circuitry?
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Traditional View
Parietal Insular Vestibular Cortex
Somatosensory Cortex
Vestibular Nuclei
Ventral Posterior Thalamus
Limbic System & Hippocampus
Vestibular Pathway to the Limbic System & Hippocampus
Papez Circuit
Entorhinal Cortex
Place CellsHD Cells
Postsubiculum Anterior Dorsal Thalamus
Lateral Mammillary Nuclei
Medial Vestibular Nucleus
Dorsal Tegmental Nucleus
Nucleus Prepositus
Alternative View for Vestibular Pathway to Limbic System
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What type of neuronal signal is projected onto Lateral Mammillary Nuclei cells from the Dorsal TegmentalNucleus?
• ~75% of cells had firing rates correlated to the animal’s angular head velocity.
• Two different types of angular head velocity correlates were found.
DTN Symmetric AHV Cells
63.6 % of AHV cells
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-400 -200 0 200 400
CW CCW
FiringRate
Angular Head Velocity (°/s)
FiringRate
Angular Head Velocity (°/s)
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-400 -200 0 200 400
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DTN Asymmetric AHV Cells
36.4 % of AHV cells
CW CCW
FiringRate
Angular Head Velocity (°/s)
FiringRate
Angular Head Velocity (°/s)
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AHV Cells
Postsubiculum Anterior DorsalThalamus
LateralMammillaryNuclei
MedialVestibularNucleus
DorsalTegmentalNucleus
NucleusPrepositus
Alternative View forVestibular Pathwayto Limbic System
HD Cells
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Neural Integrator� v dt = θ
• Starting from a known directional heading, a mathematical integration in time of angular head velocity yields angular head displacement.
• Perhaps a neural integrator, similar to the one involved in the vestibulo-ocular reflex (VOR), is present in the DTN --> LMN pathway and is responsible for generating the HD cell signal.
Working Model for integrating angular head velocity
Dorsal TegmentalNuc.
Lateral MammillaryNuc.
Anterior DorsalThalamic Nuc.
Postsubiculum
Medial VestibularNuc.
Nucleus Prepositus
Head Direction signal
Angular Head Velocitysignal
Neural Integrator ??
Interpeduncular Nuc.Medial Habenular Nuc.
Inhibitory
Excitatory
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Continuous Attractor Network
Inhibitory
Excitatory
0°
90°
180°
270°
Proposed by:Skaggs, McNaughton et al., 1995Blair, Sharp, 1995Redish, Goodridge, Touretzky, 1996, 1999Zhang, 1996
VisualInputs
Vestibular/MotorCW or CCW turns
On
OffOff
Off
Some thoughts to ponder ....
• Assume that HD cell firing arises from a continuous attractor network.
• Then removing inputs into the attractor network may either :
• a) leave the hil l of activity stationary - and a subset of HD cells from the population might be continuously active, or
• b) the hill of activity might be unstable and will drift around continuously. In this condition, we might expect to see some cells have bursts of activity as the hil l passes through the cell ’ s preferred direction.
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Our findings following vestibulardisruption showed neither prediction.
• Of 11 recorded HD cells, none of the 11 cells was tonically “on” .
• Moreover, none of the 11 cells showed bursty activity.
• Bursty activity was only seen in non-HD cells.
A. Bursty cell i n vestibular-lesioned ratB. HD cell i n normal rat
16 min recording sessions
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Navigational Systems
Landmark based Navigation:
-taking a positional fix
• Use of familiar salient external landmarks
• Episodic monitoring
Examples:
Visual, Auditory, Olfactory, Somatosensory cues
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Navigational Systems
Internal Navigation or Path Integration:
• Use of internal (idiothetic) cues resulting from movements
• Continuous monitoring
Examples:
Vestibular, Proprioceptive, Kinisthetic cues
Motor efference copy, Optic and Auditory flow
Head Direction Cells - Idiothetic Cues
Rat is placed into arenas - preferred firing direction usually shifts by > 50°
What happens when the rat walks from the cylinder into the rectangle?
?
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HD Cells use internal cues
Rat walks from cylinder into rectangle preferred firing direction shifts by a mean of ± 18°
Recording Session Sequence: Novel Conditions
Novel-Rectangle Return-Cylinder
2. Novel Session
Door open
1. Standard Cylinder
Door closed
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Standard Session
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Novel Session
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Idiothetic Cues and HD Cells
What is the influence of motor efference copy cues or optic flow in updating the cell ’s preferred direction in the Novel condition?
Idiothetic Cues and HD Cells
Cue Source Manipulation Motor Efference Passive Transport via wheeled cart Optic Flow Room Lights On/Off
Cue Source Manipulation Motor Efference Passive Transport via wheeled cart Optic Flow Room Lights On/Off
During Initial Exposure to Novel Environment:
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Idiothetic Cues and HD Cells
PASSIVE TRANSPORT
ON CART
RAT WALKS IN
ROOM LIGHTS ON
ROOM LIGHTS OFF
• all cues available • PFD maintained
• disrupts motor efference • intact optic flow • intact vestibular
• disrupts motor efference • disrupts optic flow • intact vestibular
• intact motor efference • disrupts optic flow • intact vestibular
Optic Flow
Motor Efference
Passive Transport - Room Lights Off
Head Direction (°)
Firi
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Summary of Results
PASSIVE TRANSPORT
ON CART
RAT WALKS IN
ROOM LIGHTS ON
ROOM LIGHTS OFF
Average shift of PFD: ± 65°
Average shift of PFD: ± 32°
Average shift of PFD: ± 68°
Optic Flow
Motor Efference
Average shift of PFD: ± 18°
Idiothetic Cues and HD Cells
• What do we know?
HD Cells are multi -modal:
Vestibular: Generating HD cell signal
Motor efference: Updating HD cell network
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HippocampusEntorhinal Cortex
Place Cells
HD Cells
Subiculum Postsubiculum
Lateral Mammillary Nuclei
Anterior Dorsal Thalamus
Lateral Dorsal Thalamus
Posterior Cingulate Cortex
Posterior Parietal Cortex
Motor Cortex
Medial Mammillary Nuclei
Ventral Tegmental Nucleus
Dorsal Tegmental Nucleus
Medial Vestibular Nuclei
Striatum
Landmark Sensory Information
Idiothetic Information
Visual Cortex
Other Sensory Cortex
Motor Information ?
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Head direction Cells in 3D
• HD cells fire as a function of head direction in the horizontal plane.
• But how is the horizontal reference frame defined?
• How do HD cells respond during vertical plane locomotion?
Vertical Sampling Apparatus
74 cm
Annulus
Food Cups
Wire Mesh Ladder
top view side view
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Example of Recording Protocol
MESH 0° MESH 180° MESH 270° MESH 90°
(relative to HD cell's preferred firing direction)
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Cylinder Floor and Annulus
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Mesh @ 180° Position
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Mesh @ 90° Position
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Vertical Plane Data Summary
90°
0°
-90°
-45°
45°?
?
?
+
+
+
+
+PreferredFiringDirection
Hemi-torus Model of HD Cell Firing in 3-D
270°
180°90°
0°
90°
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Horizontal Plane
Vertical Plane
-90°
Preferred Firing Direction
Cell fir ing plotted in polar coordinates
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Summary
• HD cell firing was maintained during vertical locomotion, if the rat approached the mesh in the cell 's preferred firing direction.
• Horizontal reference frame was defined by the rat’s plane of locomotion, but ……
• How does an HD cell respond when a rat locomotes in a vertical plane >90°?
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Loss of directional tuning on ceiling, with increased background firing rate.
Summary• Head direction cells are multi-modal - receiving both sensory and
motor information.
• They are observed in several areas of the brain (mostly within the limbic system).
• The vestibular system appears criti cal for generating the directional signal, but motor signals appear important for updating it.
• Brainstem circuitry involving the Dorsal Tegmental Nucleus and Nucleus Prepositus may act as an integrator for updating directional heading.
• The anterior thalamus may be a converging point for landmark and idiothetic information.
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Contr ibutors
Colleagues Postdoctoral FellowsJames Ranck, Jr., SUNY Bklyn Jeffrey Calton
Robert Muller, SUNY Bklyn Paul Dudchenko
Charles Oman, MIT Gary Muir
Robert Stackman
Graduate StudentsJoshua Bassett
Heather Burton
Jeremy Goodridge
Edward Golob
Matthew Tullman
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Session Sequence: Sensory Conflict Conditions
Conflict-Rectangle Conflict-Cylinder
4. Conflict Condition
Door open
Cylinder cue card in rotated position
3. Rotation Cylinder
Cylinder cue card in rotated position
Door closed
90° CCW Cue Rotation90° CCW Cue Rotation
Cylinder ConflictCylinder ConflictRectangle ConflictRectangle Conflict
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NovelNovel60°
66° 102°
108°
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Head Pitch Cell in LMN
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Transient Vestibular Inactivation Disrupts CA1 Place Cell Firing
Pre Post 1 hr 4 hr 12 hr
TTX
Recovery
24 hr 36 hr 48 hr 60 hr