hippocampal circuits 2

memory consolidation at different scales

synaptic consolidation - can be broadly split into two phases

early phase → does not require protein synthesis (e.g. ‘memory’ via intracellular signalling cascades, post-transductional modifications)

late phase → requires protein synthesis (e.g. via altered gene expression, synthesis of proteins that alter synaptic efficacy)

systems consolidation - post-encoding integration of initial memory trace into distributed brain circuits, lasting months to years

standard model of consolidation

the standard consolidation model (based on Marr’s 1974 model of the hippocampus) proposed that the hippocampus rapidly stores the day’s events and that the info is transferred gradually to the cortex for subsequent consolidation

the transfer process relies on the repeated reactivation of pattern of neural firing corresponding to those activated during the initial experience

plasticity within cortical circuits

encoding of perceptual, motor, and cognitive info occurs separately in several specialised primary and associative cortical circuits

plasticity in hippocampus

hippocampus knits together this information about a single experience

hippocampus driven plasticity in cortical circuits

reactivation of this hippocampal-cortical network strengthens cortico-cortical connections and allows cortical memory to become independent of the hippocampus

leads to mature intercortical connections

hippocampal storage time is limited

• rats are trained to associate a place with a shock (1 trial)

• when returned to the place of the shock they show freezing behaviour

  • this behaviour can last a lifetime

• lesions of the hippocampus produce a temporally-graded retrograde amnesia for the memory

  • loss of memories made before the lesion but no trouble forming new ones

time-dependent reorganisation of brain circuitry

metabolic activity alters different memory tests shows localisation of memory within the brain

• increasing the retention interval resulted in decreased metabolic activity in the hippocampus and increased activity in the several cortical areas

• testing in a different context at the remote time point re-engages the hippocampus, indicating the brain region that is required to encode new information

memory binding problem

cerebral cortex → processing of multi-modal info activates broadly distributed neuronal population

episodic memory in the hippocampus

features of episodic memory:

• binds together spatial, temporal, and multimodal content of an experience

• preserves temporal order of events

• allows mental ‘time travel’ - vivid, autobiographical recall

use of the trisynaptic circuit

recording single units and LFP

many in vivo, freely moving studies of the hippocampus in rodents have used tetrode recording

tetrode → bundle of 4 electrodes implanted in brain, allows single units (individual neurons) and the spikes (APs) to be isolated, along with the local field potential (LFP)

oscillations in the hippocampus

LFP recordings from hippocampus show distinct oscillations:

• theta rhythm (4-12 Hz) - during movement

• sharp wave ripples, SWR (~100-200 Hz) - during immobility and sleep

theta phase precession

encodes spatial position through firing rate (Hz) and through firing phase relative to rhythm

• place cells in CA1 signal spatial position through firing rate

• place cell recording along a linear track revealed the phase coding of spatial position

theta sequences

when an animal runs along a path going through many place fields:

• at any time during its run, the animal is likely to be within overlapping fields

• theta phase of each place cells’ firing correlated with how far the animal is through each place field

due to phase precession

• spatial order of place fields along the path

• ‘compressed’ into temporal sequence within each cycle of the theta rhythm

• brings spikes between cells within 10s of each other

  • could help to facilitate synaptic plasticity

binding multimodal experiences into episodic events

• how might the hippocampus link multimodal content from context into an episodic memory

• suggested that the hippocampus could act as a ‘sequence generator’

• may provide a spatial and temporal framework to bind together individual ‘experimental moments’ into a coherent episodic memory

replay of place cell sequences during ripples

during exploration of the environment → rat runs along a trajectory (path) through the environment. place cells representing successive positions along the trajectory fire in a specific temporal sequence as rat passes through them

during quiet wakefulness and slow-wave sleep → place cells fire in a compressed sequence again during SWR. replay can occur ‘forward’ or in ‘reverse’

importance of ripples for memory consolidation

• trained rats to find food rewards on the radial arm maze

• in the test group, they disrupted ripple in the hippocampus, via electrical stimulation to the hippocampal commissure

• in the control group, the stimulation was delayed by a random duration, so occurred after ripples

• the test group showed a memory deficit when tested later on the maze

prolonging ripple improves memories

• rhythmic optogenetic stimulation of CA1 at ripple frequency was used to artificially prolong ripple

• tested rats on an alternating M-maze task where the rat has to remember which arm it had chosen last after a 20sec delay

• ripple prolongation improved working memory over delays compared to control group

SWR generation

• CA3 is important for SWR initiation

• recurrent excitation between CA3 pyramidal cells generates synchronous population bursts, driving pyramidal cells and interneurons in CA1

• recent theories suggest that rapid oscillatory firing activity in CA1 is generated via:

  • reciprocal inhibition between interneurons, which sets the ripple rhythm via rapid GABAA receptor mediated inhibition / disinhibition

  • pyramidal cell firing drives the ripples, paced by reciprocal pyramidal-interneuron feedback inhibition loops

what happens during sleep

REM → vivid dreams, 90-120 min/night, important in procedural and emotion related memory consolidation

NREM → including slow wave sleep- important in declarative memory consolidation

slow waves (0.5-4.0 Hz)

• characterise slow wave sleep = NREM sleep stages 3 and 4

• generated in cortical circuits

• organise cortical activity into up (active) and down (silent) states

spindle oscillation (12-15 Hz)

• generated in the thalamus and modulated by thalamo-cortical circuits

• coordinate synchrony of cortical and hippocampal neuron activity

ripples (80-140 Hz)

• generated in hippocampus

• structure replay of memory traces

nested oscillations coordinate hippocampus and cortex during sleep

• synchronisation of spindles to slow wave up-state and of ripples to troughs of spindles

• this triple nesting of oscillations could provide precision temporal coordination of hippocampal and cortical neuronal activity during sleep for consolidation

coordinated activity in hippocampus + visual cortex

• rats run around a figure eight shaped maze finding food alternately at L and R

• place cells are recorded in CA1 and visual cortex

• consistency of firing field of cells in cortex and hippocampus along route over two days

• overlapping spatially localised firing of hippocampus and cortical cells during training runs

replay of coordinated activity during sleep

• these routes are replayed during sleep

• groups of cells in cortex and hippocampus fire in the same order during slow wave sleep as when rats runs laps around the track

• correlated replay activity in cortex and hippocampus during sleep

• could underlie consolidation of memories during sleep