Neurones and Memory Storage Flashcards
Hebbian cell assemblies
Cells assemblies in which memories and other cognitive functions are represented
Reverberatory circuits
Diffuse structures comprising cells in the cortex and diencephalon (and also, perhaps, in the basal ganglia of the cerebrum), capable of acting briefly as a closed system
The engram can be described as…
…a reverberatory transient trace
Working memory (STM)
Persistent activity in the prefrontal and higher cortical areas, “the memory buffer” + theta & gamma activity
STM –> LTM transition
Conversion of persistent activity into a latent memory trace by the hippocampal formation
LTM
Consolidated and redistributed across the neocortex, and so is eventually no longer dependent upon the hippocampus. (patient HM)
DMTS task and the hippocampus
Four types of neuronal response behaviour were seen in the CA3 or CA1 region of hippocampus matching the different phases
Other brain areas associated with working memory
Prefrontal, motor and entorhinal cortices, also have a subgroup of neurones that fire during the “delay phase” of DMTS tasks again suggesting they “store” information or a representation in that brain area
Neurophysiology of PFC during working memory
Many PFC neurons appearing to maintain information about spatial or object cues during the “delay periods” (of a DMTS task)
Why is STM also referred to as “online” memory?
Persistent cortical activity during delayed task is a characteristic feature of working memory
What does the persistent cortical activity during WM represent?
An internally driven “stored information” about: sensory stimuli; an intended action (decision or motor response); an item recalled from long-term memory (LTM)
Substrates for persistent activity
Basal ganglia-thalamocortical loops
Reciprocal loops between cortical areas
Local recurrent excitatory cortical network
(+ve fb loops^, learn diagrams)
Biophysical- membrane potential bistability
Example of membrane potential instability
e.g. entorhinal cortex
Small brief inputs/changes in membrane current → switch
between two stable membrane potentials (Egorov et al. 2002)
Activation or inactivation of inward (depolarizing) currents
ICAN switched on by mAChRs - role of ACh in memory
Neuropharmacology of persistent cortical activity
Delayed reaching task, type of DMTS
Hold down a key to initiate trial
• After a short delay, one of two target switches is briefly
illuminated - “Cue” (Inst. Stimulus on right).
• Longer “Delay period” - waiting for the “Go signal” (using
working memory - which button do I need to press?)
• Given “Go signal” and can now release key and reach and press the cued switch i.e. “Match”
• Get a reward - a sip of fruit juice!
Record what’s happening in the motor cortex:
Much greater contribution of NMDA-Rs
than of non-NMDA-Rs (AMPA-Rs)
Characterisation of NMDA mediated responses
slow kinetics and little desensitization → stable long lasting depolarization during persistent synaptic activation
Activation of D1-Rs in rat PFC deep layer pyramidal cells
Activation of D1-Rs (SKF38393 D1-R selective agonist → up regulation of NMDA-R function (enhances channel function and trafficking) → “up states” - periods of persistent network activity (rat prefrontal cortex deep layer pyramidal cells)
Functional evidence of synergism between DA and Glu systems regarding persistent cortical activity
Low doses of NMDA-R and D1-R antagonists which are ineffective alone, produce profound reduction in learning tasks when used in combined in rats
NMDA-R antagonists on WM
inhibit working memory in humans
Short term D1-R activation
improves working memory in aged primates
Organisation of persistent cortical activity
The binding problem-
Theta and gamma waves orchestrate the timing of synchronous neuronal activity across networks
Gamma and theta waves in episodic/spatial memory
Sequence presented over 5-9 gamma cycles (30-80Hz)
Repeated over several theta cycles with changes in the sequence representing the spatiotemporal relationship of the component parts (4-10Hz)
Gamma oscillation - ensures the precise time of firing in a subset of pyramidal neurones through fast membrane potential depolarization over 10-30ms time scale
Theta oscillation - a carrier wave that organizes information about a moment in time and synchrony across hippocampus and other cortical areas
Types of CA1 gamma in freely moving awake rats
CA3 Schaffer input → CA1 slow <60Hz
EC PP input → CA1 fast >60Hz
Occur at different phase of theta cycle
Importance of segregating CA3 and EC input?
Citical for preventing interference from previously learned associations (via
CA3) during encoding of new associations (via EC)
Inducing gamma oscillations in rodent hippocampal slices
DNQX, carbachol, bicuculline
Fisahn 2004
Modelling theta: background in vivo (rodent)
Prominent in area CA1 – slm (rat)
Initially thought to be dependent on input from the medial septal nucleus and diagonal band of Broca:
both GABAergic + Cholinergic
Lesioning these structures prevents theta
In CA1: there are two locations where
hippocampal theta is generated in vivo: slm: EC PP input → CA1
sr: CA3 Schaffer input → CA1
Hebb’s rule
In principle, this rule allows for the selective association of those presynaptic inputs (including that from cell A) that take part in the sustained co-activation of the post-synaptic neurone (cell B) through a selective increase in their synaptic efficiency.
Non-active inputs do not undergo this change in efficiency
