Transcript ppt

Sum of the Parts:
Musings on the Function of the
Hippocampo-Entorhinal System
NaK Group
September 24, 2003
“Computational models of the
hippocampal region: linking
incremental and episodic memory”
MA Gluck, M Meeter and C.E. Myers
TRENDS in Cognitive Sciences
June 2003
Connection Overview
Interesting Features:
Layer II perforant
path splits: one to DG,
one to CA3
Layer III projects to
CA1
Unidirectional
“Tri-synaptic Circuit”
Incremental (Multiple Trial) Learning:
Gluck and Myers
Hippo system performs info processing that
transforms stimulus representations according to
specific rules with series of connected nets
Compresses (makes similar) co-current or redundant
input
Differentiates inputs that predict different future events
Passes new assemblies to LTM networks in the neocortex
and cerebellum, where error between predicted
(idealized or random) hippo output and actual output is
used to update weights
Recently, specifically proposed EC’s anatomy and
physiology could compress representations of cocurrent stimuli
Incremental Learning (Multiple Trials):
Schmajuk and DiCarlo
Hippo region crucial for forming new
stimulus configs (A and B diff from AB)
Cortex combines cue info to allow configural
learning, then cerebellum learns to map this
configural info into a behavior
Hippo region calculates error between
prediction and actual, then sends the error
measure to neocortex and cerebellum, as well
as sending predictions to cerebellum
Recently, proposed that the prediction
signal, used by the hippo region,
originates in the EC
Episodic (One Time) Memory Models
Stores random vectors (not unreasonable since info may only
appear once)
Hippo system orthogonalizes conjunctive, overlapping,
neocortical patterns by forming relatively sparse patterns,
reducing interference from similar memories
Using computational arguments, this storage may be
temporary (during theta), with older memories passed to the
neocortex (during SPWs)
GABAergic modulation has been argued to facilitate encoding
new memories while not interfering with retrieval of old
Hippo system may also play a role in sequence learning and
spatial navigation
Episodic Memory:
Brain Substrates
CA3
Ideal for binding diff parts of
one pattern (autoassociative)
or binding diff patterns in
sequence (heteroassociative),
due to high recurrent
collateral
CA1
“Decodes” hippo patterns,
allowing association with the
cortical pattern from which it
originated
May be a pattern separator
Dentate Gyrus
“Sparsifier” enabling pattern
separation
Entorhinal Cortex
May extract regularities of
longer time intervals, forming
a familiarity signal
“Physiological patterns in the
Hippocampo-entorhinal
cortex system”
JJ Chrobak, A Lorincz and G Buzsaki
HIPPOCAMPUS
2000
Theta and Sharp Waves
Theta Waves
Seen during exploration,
sensory input, etc.
EC Layer II and III
neurons fire in thetamodulated gamma freq,
projecting to the
dentate, CA3, CA1, and
the subiculum
Dentate and CA1
neurons also
independently fire thetamodulated gamma as
they receive EC input
EC Layers V and IV are
relatively quiet
Thought to allow EC
neurons to alter synaptic
connectivity in the hippo
Sharp Waves
Seen during
consummatory
behaviors, sitting quietly,
etc.
EC Layers V and IV
neurons fire 140-200 Hz
as they receive sharp
waves from the hippo
(originating primarily in
CA3)
This discharge coincides
with neocortical activity
(perirhinal and medial
prefrontal cortexes)
EC Layers II and III do
not increase their firing
rates
Thought to allow hippo
neurons to alter
connectivity of
neocortical neurons
EC to Hippocampus Projections
EC Layer II project to DG and CA3 by
perforant path
Stellate cells and pyr cells form islands, which may
represent functional clusters
Stellates exhibit theta-freq, sub-threshold membrane
oscillations, firing (gamma) spike clusters on
depolarizing phases, conveying patterns to DG/hippo
targets
EC Layer III projects to CA1 and Subiculum
Primarily pyr cells, similar to neocortical neurons
Possibly “high fidelity” pattern transmitters of cortical
input
Hippocampus to EC Projections
Layer V and IV are primary receivers of hippo
output, which then project to cortical,
subcortical (amygdala, septum, etc.) targets,
and Layers II and III
Occurring primarily during SPWs
Layer III only slightly increased their firing rates and
Layer II showed no change
Experimental stimulation of deep layers
produces inhibition of superficial layers
Lesion of Layer III will allow propogation of
epileptiform bursts from deep layers to Layer
II, implying Layer III may act as a “gate”
The gating may be controlled by input from the
amygdala, which projects to Layers III and V and is
excited by SPWs via CA1
Working Together:
EC-Hippocampal Cooperation
“Novelty” (error)detecting
“reconstruction
network”
Assumptions:
Neocortical patterns
are primarily projected
to the hippo via Layer
III
The hippo reconstructs
the neocortical
template in order to
optimize the pattern
into temporal
sequences
Layer II compares
neocortical inputs and
feedback inputs from
the hippocampus
Steps:
1.
2.
3.
4.
Primary input from the
neocortex and Layer Vtransformed output from
the hippocampus is
compared by Layer II
Layer II “calculates”
error or novelty, and this
is sent to the DG and
CA3, where alterations
(plasticity) occur in the
CA3 network
If there is no novelty,
then the hippocampus
simply reproduces
previously stored
patterns
This will continue until
the error is minimized
Working Together:
Summary
“Hippocampus as comparator: role
of two input and two output systems
of the hippocampus in selection and
registration of information”
OS Vinagradova
HIPPOCAMPUS
2001
Two Inputs
Reticulo-Septal
“Attention” mechanism
Theta-modulated, allowing “packeting”
May organize hippocampal responses to
sensory input and protect them from
interference
Cortico-Hippocampal
Cortical areas, as well as EC, areas gather
sensory info
DG prelim “mixer,” that generalizes and
simplifies (sparsifies?) the signal before CA3
Two Outputs
CA3 to
Septum (and on to the brain stem)
Regulates level of arousal by inhibiting the Reticular Formation
During novel stimulus, the RF is released (arousal) due to
decreased output of CA3, which is being used for processing and
therefore subject to more inhibitory control
When novelty is lost, CA3 activity increases again, suppressing RF
CA1
Schaffer Collateral as “filter”
Thought to shunt dendritic APs, possibly through local I cells,
blocking cortical signals
Only CA1 cells not receiving CA3 input participate in processing
and transmission
CA1-Subiculum to Limbic Circuit to Neocortex
Encoding preserved as outputs and more differentiated the
farther away from hippo
This additional processing may be crucial for permanent
storage in cortex
Putting It All Together
CA3 “compares” cortical (via DG) and brain
stem (via Septum) inputs
1. In constant state (no cortical input), CA3 indirectly
suppresses RF
2. Change causes regulatory inhibition to dominate CA3,
which releases RF
Theta activated
Cortical pathways to some CA1 cells blocked
3. Cortical signal develops with delay
CA3 response starts to habituate
CA1 output passes to limbic circuit, which is additionally
processed at each higher level and eventually stored
4. CA3 completely habituates as novelty is lost, returning
the system to “closed” state
5. If familiar signal appears, the system briefly “opens”
again, but quickly closes
Comparator System