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6BBYN309 Memory Mechanisms in Health and Disease JC2 Essay £13.46
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6BBYN309 Memory Mechanisms in Health and Disease JC2 Essay

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This is the essay I wrote for the paper "A disinhibitory microcircuit for associative fear learning in the auditory cortex". This paper got 80%. Hope it helps.

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  • January 23, 2025
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JC2 Essay

a) The researchers investigated how specific interneurons within the first three layers of
the auditory cortex facilitate fear memory formation, focusing on whether
disinhibition of pyramidal neurons, located primarily in layers 2/3, driven layer 1 (L1)
interneurons activation, is essential for associating a conditioned auditory cue (CS)
with an aversive foot shock (UCS). During fear conditioning, foot shocks activate
cholinergic afferents from the basal forebrain, which in turn activate L1 interneurons.
These L1 interneurons inhibit parvalbumin-positive (PV+) interneurons in layer 2/3,
resulting in the disinhibition/activation of pyramidal neurons. This disinhibition
enhances the cortical response to conditioned auditory stimuli, indicating that
pyramidal neurons encode both the sensory cue and its aversive significance, thereby
facilitating associative fear learning.

The researchers used pharmacological methods with nAChR antagonists
(mecamylamine and methyllycaconitine) to block cholinergic activation of L1
interneurons, reducing fear responses and confirming the importance of cholinergic
signalling in disinhibition (Fig. 5b). In an optogenetic experiment, PV+ interneurons
were selectively stimulated during the foot shock period, counteracting L1-driven
disinhibition. Mice subjected to this intervention showed a drastic reduction in fear
responses (Fig. 5f), demonstrating that pyramidal neuron disinhibition during the
unconditioned stimulus is crucial for associative fear memory formation.




b) Figure 5 directly addresses the central question of the study: how disinhibition of
pyramidal neurons by PV+ interneurons influences fear learning within the auditory
cortex. Panels a and b establish that activation of nAChRs by acetylcholine is essential
for fear conditioning in the auditory cortex. This conclusion is supported by findings
that mice injected with nAChR antagonists MEC and MLA before conditioning
exhibited significantly lower freezing responses to the CS+ compared to
vehicle-treated controls. These results highlight that the initial step of the
disinhibitory microcircuit, ACh activation of nAChRs in L1 interneurons, is crucial for
initiating fear learning.

Panels c through f demonstrate the importance of inhibiting PV+ interneurons in
layer 2/3, necessary for disinhibition and activation of pyramidal neurons. Panel f
shows that optogenetic stimulation of PV+ interneurons during conditioning, via
channelrhodopsin-2, disrupts disinhibition and reduces freezing responses to the

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