Neurones and Memory Storage

Question 1

Hebbian cell assemblies

Answer 1

Cells assemblies in which memories and other cognitive functions are represented

Question 2

Reverberatory circuits

Answer 2

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

Question 3

The engram can be described as…

Answer 3

…a reverberatory transient trace

Question 4

Working memory (STM)

Answer 4

Persistent activity in the prefrontal and higher cortical areas, “the memory buffer” + theta & gamma activity

Question 5

STM –> LTM transition

Answer 5

Conversion of persistent activity into a latent memory trace by the hippocampal formation

Question 6

LTM

Answer 6

Consolidated and redistributed across the neocortex, and so is eventually no longer dependent upon the hippocampus. (patient HM)

Question 7

DMTS task and the hippocampus

Answer 7

Four types of neuronal response behaviour were seen in the CA3 or CA1 region of hippocampus matching the different phases

Question 8

Other brain areas associated with working memory

Answer 8

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

Question 9

Neurophysiology of PFC during working memory

Answer 9

Many PFC neurons appearing to maintain information about spatial or object cues during the “delay periods” (of a DMTS task)

Question 10

Why is STM also referred to as “online” memory?

Answer 10

Persistent cortical activity during delayed task is a characteristic feature of working memory

Question 11

What does the persistent cortical activity during WM represent?

Answer 11

An internally driven “stored information” about: sensory stimuli; an intended action (decision or motor response); an item recalled from long-term memory (LTM)

Question 12

Substrates for persistent activity

Answer 12

Basal ganglia-thalamocortical loops
Reciprocal loops between cortical areas
Local recurrent excitatory cortical network
(+ve fb loops^, learn diagrams)
Biophysical- membrane potential bistability

Question 13

Example of membrane potential instability

Answer 13

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

Question 14

Neuropharmacology of persistent cortical activity

Answer 14

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)

Question 15

Characterisation of NMDA mediated responses

Answer 15

slow kinetics and little desensitization → stable long lasting depolarization during persistent synaptic activation

Question 16

Activation of D1-Rs in rat PFC deep layer pyramidal cells

Answer 16

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)

Question 17

Functional evidence of synergism between DA and Glu systems regarding persistent cortical activity

Answer 17

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

Question 18

NMDA-R antagonists on WM

Answer 18

inhibit working memory in humans

Question 19

Short term D1-R activation

Answer 19

improves working memory in aged primates

Question 20

Organisation of persistent cortical activity

Answer 20

The binding problem-

Theta and gamma waves orchestrate the timing of synchronous neuronal activity across networks

Question 21

Gamma and theta waves in episodic/spatial memory

Answer 21

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

Question 22

Types of CA1 gamma in freely moving awake rats

Answer 22

CA3 Schaffer input → CA1 slow <60Hz
EC PP input → CA1 fast >60Hz
Occur at different phase of theta cycle

Question 23

Importance of segregating CA3 and EC input?

Answer 23

Citical for preventing interference from previously learned associations (via
CA3) during encoding of new associations (via EC)

Question 24

Inducing gamma oscillations in rodent hippocampal slices

Answer 24

DNQX, carbachol, bicuculline

Fisahn 2004

Question 25

Modelling theta: background in vivo (rodent)

Answer 25

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

Question 26

Hebb’s rule

Answer 26

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