🪴 Jacky Zhao's Quartz 4.0

Search

SearchSearch

PV, SOM and VIP

Nov 11, 20247 min read

A disinhibitory microcircuit for associative fear learning in the auditory cortex | Nature

To test directly the role of auditory cortex in this paradigm, we inhibited neuronal activity during fear conditioning by local injection of the GABAA (c-aminobutyric acid)-receptor agonist muscimol into the auditory cortex (Fig. 1a and Supplementary Fig. 1). When tested 24 h later in a drug-free state, this manipulation resulted in strongly reduced fear levels (Fig. 1b), indicating that activity in auditory cortex is required for fear learning in this paradigm.

inhibition auditory cortex neurons ⇒ mouse doesn’t learn.

mouse doesn’t hear well ⇒ so it can’t learn?

Tone with shock

Basal forebrain → L1 : activate using Ach

L1 →(normal) PV L2/3 → Exc : Tone

L1 → (inhibit strongly ⇒ causing disinhibition of Exc)PV L2/3 → Exc : Tone with shock

This disinhibition is important for fear learning, the inhibition masks the fear part. When no disinhi, less fear

in L1 a large part of them are GABA

L1 interneurons may be a general feature of neocortical organization

  • Rapid Rebalancing of Excitation and Inhibition byCortical Circuitry

Rapid Rebalancing of Excitation and Inhibition by Cortical Circuitry | Elsevier Enhanced Reader Activating archaerhodopsin in PV+ neurons effectively suppressed them in layer 4. How- ever, the resulting increase in excitation outweighed Arch suppression and produced a net increase in PV+ activity in downstream layers.

suppressing PV+ neurons did not reduce inhibition to principal neurons (PNs) but instead resulted in a tightly coordinated increase in both excitation and inhibition.

The suppression of PV+ activity in L4 led to an increase in excitatory drive to neurons downstream of L4, which outweighed the suppressive effect of Arch and produced a net increase in PV+ spiking.

PV → PC, PC → PV

PV supressed with arch ⇒ PV rate decreases ⇒ PC increases ⇒ PC activates PV more ⇒ PV increases (effect of PC activation > Arch supresssion)

Supress PV ⇒ PC activity increases. Reasons could be

  1. inhibition decrease bcoz PV off
  2. PC increase bcoz PV off ⇒ PC inc ⇒ PC give more current to PC

to know 1 or 2, measure epsc and ipsc.

expected - ipsc dec and epsc inc

actually - both epsc and ipsc inc.

both epsc and ipsc increased by same factor,

⇒ rebalance occuring in the circuitry, if PV off, PC inc activating PV, PV on, all normal except both exc and inh increase

now if pre-syn current inc, 2 reasons -

  1. pre syn spikes inc
  2. synchronisation

to check integral of the postsynaptic current (total charge, QE and QI) ⇒

which scales with the number of presynaptic spikes, independent of their timing

WHY THIS?

n summary, we found that broadly suppressing PV+ activity did not reduce inhibition to PNs but instead produced a tightly coordinated increase in both excitation and inhibition, in which all major features of excitatory-inhibitory interactions—amplitude ratio, relative timing, and co-tuning—were preserved

So if PV is off, circuit is almost the same, which things both exc and inh elevated.

Green - PV

Red - PV off

The same cells showed a 5.0 – 2.7-ms decrease in median spike latency, a hallmark of increased excitatory drive

There are networks of neurons. Network consists of pv, PC. these networks could be in different layers or in the same horizontal layer.

Supress pv in one ⇒ in that network, u will find pv rate dec, pc rate inc

but pc projecting into diff network ⇒ pv rate inc and pc rate inc in that different network. reason - pc inc will inc epsc in pc of next layer, pc inc will also increase ipsc in pv of next layer.

  • Disinhibition, a Circuit Mechanism for Associative Learning and Memory

Disinhibition, a Circuit Mechanism for Associative Learning and Memory | Elsevier Enhanced Reader

Young idea - inhibition pathways are disinhibited for sake of learning

Disinhibition improves:-

disinhibition improved memory - Involvement of the amygdala GABAergic system in the modulation of memory storage - ScienceDirect

inhibition improves -

Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition

  • Amplifying the redistribution of somato-dendritic inhibition by the interplay of three interneuron types

Amplifying the redistribution of somato-dendritic inhibition by the interplay of three interneuron types | PLOS Computational Biology

  1. Parvalbumin-expressing (PV) interneurons preferably inhibit the perisomatic regions and the basal dendrites of exc(pryramidal cell)
  2. somatostatin-expressing (SOM) neurons mainly target the apical dendrites of PCs
  3. vasoactive intestinal peptide (VIP) mainly connects to the dendrite-targeting SOM neurons, thereby providing a disinhibitory circuit for the distal dendrite of PCs

While top-down feedback is associated with internal predictions, bottom-up connections are thought to carry information from the external world

Connection prob: SOM largely inhibits PV, next PC, next VIP(receiprocal connections between VIP and PV).

VIP controls whether to integrate or cancel bottom up and top down inputs

When the network is in the “switch” regime, we found that small changes in VIP input are sufficient to switch the network between two computational states in which top-down inputs are either transmitted or cancelled entirely

VIP and Mismatch

Visuomotor Coupling Shapes the Functional Development of Mouse Visual Cortex | Elsevier Enhanced Reader

there are some neurons - Mismatch neurons(MM), fire highly when predictions ≠ sensory input

After experience SOM and MM have connections, SOM receives sensory input

VIP receives predictions if predictions == sensory input VIP remains off

SOM inhibits MM neurons ⇒ MM neurons don’t fire

if predictions ≠ sensory input

VIP(that receive predictions) active. VIP turns off SOM

MM don’t receive inhibition from SOM, MM fire

end

  • Somatostatin interneurons in auditory cortex regulate cortical representations and contribute to auditory perception

Somatostatin interneurons in auditory cortex regulate cortical representations and contribute to auditory perception | bioRxiv

46 SOM interneurons from layer 2/3 (L2/3) of mouse auditory cortex during task performance, and observed large evoked calcium transients in SOM interneurons during task performance

either selective to tone frequencies or to categorical choices (Figure 1D ).

todo

  • 1 E and F - ROC

scaling of the tuning curve (type II) is likely to have an effect on stimulus detection

som on in type - 1 → stimulus discrimination

som off in type -2 → stimulus detection

Graph View

Backlinks