A cortical circuit for gain control by behavioral state

A cortical circuit for gain control by behavioral state Fu Tucciarone Espinosa Sheng Darcy Nicoll Huang Stryker

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A cortical circuit for gain control by behavioral state 2014 Cell 10.1016/j.cell.2014.01.050 Fu2014-a-cortical-circuit-for-gain-control-by-behav Fu2014-a-cortical-circuit-for-gain-control-by-behav.txt, the project's staged copy 85c8d4b183fbda241baa94fdd4a74882cf907589 not-redistributable neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them the circuit by which locomotion increases visual responses in mouse V1 Quotation withheld because this record is not cleared for redistribution. what pathway carries behavioural state into sensory cortex to produce the gain change Quotation withheld because this record is not cleared for redistribution. identifies VIP interneurons as the necessary and sufficient element, driven by nicotinic input from basal forebrain, and proposes the circuit as a general mechanism for state-dependent cortical gain control Quotation withheld because this record is not cleared for redistribution. mechanism Quotation withheld because this record is not cleared for redistribution. locomotion-driven gain modulation of visual cortex Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms Locomotion drives VIP interneurons, which inhibit SST interneurons, thereby disinhibiting neighbouring excitatory cells and raising their visual gain Quotation withheld because this record is not cleared for redistribution. mechanisms Acetylcholine released from basal forebrain depolarises VIP neurons directly via nicotinic receptors, carrying the behavioural-state signal into cortex Quotation withheld because this record is not cleared for redistribution. mechanisms PV neurons show mixed locomotion responses because their change is a second-order consequence of SST disinhibition rather than direct locomotor drive Quotation withheld because this record is not cleared for redistribution. VIP neurons inhibit SST neurons, releasing neighbouring excitatory cells - a disinhibitory circuit Quotation withheld because this record is not cleared for redistribution. acetylcholine from the nucleus of the diagonal band depolarises VIP neurons directly through nicotinic receptors Quotation withheld because this record is not cleared for redistribution. PV heterogeneity is explained as a secondary effect: VIP inhibits SST, SST inhibits PV, and PV also receives local excitation Quotation withheld because this record is not cleared for redistribution. the state signal is carried by a pathway distinct from the sensory one, which is why VIP responses persist in darkness Quotation withheld because this record is not cleared for redistribution. the kinetics are slow and lack a fast component, so the receptor is likely non-alpha7 nicotinic Quotation withheld because this record is not cleared for redistribution. photolytic damage of individual VIP cells by restricting the excitation beam to one cell diameter at a time, sparing nearby cells Quotation withheld because this record is not cleared for redistribution. Nicotinic blockade did not fully abolish the locomotion response, so other inputs must contribute. what this limits: the sufficiency of the nicotinic account: THE RESPONSE OF VIP NEURONS TO LOCOMOTION ... WAS NOT COMPLETELY ABOLISHED BY NACHRS ANTAGONISTS, INDICATING THAT other inputs contribute Quotation withheld because this record is not cleared for redistribution. Rabies tracing is inefficient, so additional neuromodulatory inputs may have gone undetected. what this limits: the completeness of the input map only: inputs MIGHT NOT BE REVEALED DUE TO THE LOW EFFICIENCY OF rabies tracing Quotation withheld because this record is not cleared for redistribution. In the barrel-cortex experiment whiskers were not immobilised, so sensory input was not fully removed. what this limits: the barrel-cortex control specifically: ALTHOUGH THE MICE WERE RUNNING IN DARKNESS WITH NO VISUAL INPUT, THE WHISKERS WERE INTACT AND THE MICE WERE FREE TO MOVE THEM - the sensory input was not actually removed Quotation withheld because this record is not cleared for redistribution. The auditory-cortex recordings were made without adequate isolation of auditory input. what this limits: the auditory-cortex recordings only: auditory input was not adequately isolated, so the modality-general reading of those data is not supported by that experiment Quotation withheld because this record is not cleared for redistribution. nicotinic blockade did not completely abolish the locomotion response, so other inputs exist duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - nicotinic blockade did not completely abolish the locomotion response, so other inputs contribute Quotation withheld because this record is not cleared for redistribution. rabies tracing is low-efficiency, so other neuromodulatory inputs may simply not have been revealed what this limits: the same scope as limitations[1] - rabies tracing is low-efficiency, so inputs may simply not have been revealed Quotation withheld because this record is not cleared for redistribution. in the barrel cortex experiment the whiskers were intact and free to move, so the result may not isolate locomotion duplicate of: limitations[2] · what this limits: the same scope as limitations[2] - in the barrel-cortex experiment the whiskers were intact and free to move, so sensory input was not fully removed Quotation withheld because this record is not cleared for redistribution. the auditory setup was far from ideal at isolating auditory input what this limits: the same scope as limitations[3] - the auditory setup was far from ideal at isolating auditory input Quotation withheld because this record is not cleared for redistribution. the basal forebrain responds to many things besides locomotion, including females and water what this limits: the locomotion-specificity of the basal forebrain account: THE BASAL FOREBRAIN RESPONDS TO MANY DIFFERENT STIMULI AND MAY INFLUENCE CORTICAL RESPONSE BY MODULATING DIFFERENT POPULATIONS OF NEURONS Quotation withheld because this record is not cleared for redistribution. other groups report different effects of locomotion on SST neurons what this limits: the agreement with the wider literature on SST cells: DIFFERENT EFFECTS ON SST NEURONS HAVE ALSO BEEN REPORTED elsewhere, so the consensus this result matches is not unanimous Quotation withheld because this record is not cleared for redistribution. the SST-hyperpolarisation-during-whisking result, used as evidence that the same circuit may run in another modality Quotation withheld because this record is not cleared for redistribution. rabies virus monosynaptic retrograde tracing, imported to find the afferents of a genetically defined cell type Quotation withheld because this record is not cleared for redistribution. identified inhibitory neuron types recorded during stationary periods and locomotion, with and without visual stimulation, and compared against unlabelled neurons in the same recordings eliminates: a change that follows from locomotion or from the visual stimulus alone rather than from the cell type - the unlabelled neurons see the same two manipulations · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. gain control here means a multiplicative change in visual response with no change in orientation selectivity - the OSI is checked and unchanged in both the locomotion and the optogenetic case Quotation withheld because this record is not cleared for redistribution. behavioural state is operationalised as running speed on a floating ball, with stationary and running separated at 1 cm/s Quotation withheld because this record is not cleared for redistribution. central rather than peripheral is established by a negative control in LGN, not by an argument Quotation withheld because this record is not cleared for redistribution. VIP, SST and PV are genetic labels here, not physiological inferences - the paper says electrophysiology alone cannot distinguish these cell types Quotation withheld because this record is not cleared for redistribution. claim_type: mechanism a second reading reaching the same value. Recorded: mechanism — note: a second reading reaching the same value from a different sentence. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: two-photon calcium imaging in running head-fixed mice, local pharmacology, slice recording, rabies retrograde tracing, optogenetic activation and photolytic ablation a second reading DIFFERING from the recorded value. Recorded: electrophysiology — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: behavioural-state gain control in sensory cortex a second reading DIFFERING from the recorded value. Recorded: locomotion-driven gain modulation of visual cortex — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. replicates → Niell and Stryker, 2010 Quotation withheld because this record is not cleared for redistribution. builds-on → Pfeffer et al., 2013 Quotation withheld because this record is not cleared for redistribution. extends → Lee et al., 2010 Quotation withheld because this record is not cleared for redistribution. synthesises-with → Pi et al. 2013 on VIP disinhibition in prefrontal and auditory cortex - a paper independently tagged in this corpus Quotation withheld because this record is not cleared for redistribution. extends → Niell and Stryker's finding that locomotion increases V1 gain without changing selectivity Quotation withheld because this record is not cleared for redistribution. supports → Pfeffer et al. on VIP neurons inhibiting SST neurons Quotation withheld because this record is not cleared for redistribution. contradicts → the expectation of substantial direct motor cortex input to V1 VIP neurons Quotation withheld because this record is not cleared for redistribution. distinguishes-from → the run-onset neurons of Keller et al., which respond only transiently differs in: THE AXIS IS TRANSIENT VERSUS SUSTAINED RESPONSE. 'Quotation withheld, while we find that VIP neurons resp[ond throughout].' The identification of a cell class in an earlier paper is disputed on a response-time-course criterion - so the two literatures may be about different populations, and only the time course says so. Quotation withheld because this record is not cleared for redistribution. qualifies → its own cholinergic account, by noting noradrenergic input as a likely additional source Quotation withheld because this record is not cleared for redistribution. VIP —causes→ SST VIP SST strength of the relation: 0.95 · note: inhibits. and the same quote records that other groups report different effects on SST - the disagreement travels with the edge Quotation withheld because this record is not cleared for redistribution. locomotion —causes→ VIP locomotion VIP strength of the relation: 0.95 Quotation withheld because this record is not cleared for redistribution. basal forebrain —causes→ VIP basal forebrain VIP strength of the relation: 0.9 · note: largely through nicotinic inputs; blockade cut the response by more than two thirds but did not abolish it Quotation withheld because this record is not cleared for redistribution. VIP —causes→ gain control VIP gain control strength of the relation: 1 · note: the rare corpus case where BOTH necessity and sufficiency are demonstrated rather than inferred Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but VIP activation is necessary and sufficient for the locomotion-induced INCREASE in visual response; 'gain control' is not in the span. Quotation withheld because this record is not cleared for redistribution. SST —causes→ PV SST PV strength of the relation: 0.8 · note: inhibits; invoked to explain why PV responses are heterogeneous rather than uniform Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. Mann-Whitney U test Mann-Whitney U test Quotation withheld because this record is not cleared for redistribution. paired t-test paired t-test Quotation withheld because this record is not cleared for redistribution. ANOVA ANOVA Quotation withheld because this record is not cleared for redistribution. Wilcoxon rank-sum test Wilcoxon rank-sum test Quotation withheld because this record is not cleared for redistribution. Wilcoxon signed-rank test Wilcoxon signed-rank test Quotation withheld because this record is not cleared for redistribution. standard error of the mean standard error of the mean Quotation withheld because this record is not cleared for redistribution. zero-time cross-correlation zero-time cross-correlation Quotation withheld because this record is not cleared for redistribution. Mann-Whitney U-test Mann-Whitney U-test Quotation withheld because this record is not cleared for redistribution. paired Wilcoxon signed rank test paired Wilcoxon signed rank test Quotation withheld because this record is not cleared for redistribution. one-way ANOVA one-way ANOVA Quotation withheld because this record is not cleared for redistribution. VIP neurons in mouse V1 are activated in tight correlation with locomotion even in complete darkness, unlike nearly all neighbouring non-VIP neurons. Quotation withheld because this record is not cleared for redistribution. Visual stimulation did not increase but significantly reduced the cross-correlation between VIP activity and locomotion. Quotation withheld because this record is not cleared for redistribution. SST neuron activity was on average negatively correlated with locomotion at time zero. Quotation withheld because this record is not cleared for redistribution. Blocking nicotinic cholinergic receptors locally in V1 removed most of the VIP locomotion response, while blocking glutamatergic input did not. Quotation withheld because this record is not cleared for redistribution. Monosynaptic rabies tracing identified the cholinergic nucleus of the diagonal band of Broca in basal forebrain as a direct input source to upper-layer V1 VIP neurons. Quotation withheld because this record is not cleared for redistribution. Optogenetically driving VIP neurons in stationary mice reproduced the locomotion-induced gain increase, and selectively killing VIP neurons removed it. Quotation withheld because this record is not cleared for redistribution. The gain-and-loss experiments together establish VIP activation as both necessary and sufficient for the locomotion-driven enhancement of excitatory visual responses. Quotation withheld because this record is not cleared for redistribution. VIP neuron responses in primary auditory cortex were also associated with locomotor activity. Quotation withheld because this record is not cleared for redistribution. Running increases visual responses without changing orientation selectivity. Quotation withheld because this record is not cleared for redistribution. VIP neurons track locomotion in complete darkness, when neighbouring neurons show only spontaneous activity Quotation withheld because this record is not cleared for redistribution. VIP neurons are the majority of locomotion-responsive cells in V1 in the absence of visual stimulation Quotation withheld because this record is not cleared for redistribution. visual stimulation does not increase, and in fact reduces, the coupling between VIP activity and locomotion Quotation withheld because this record is not cleared for redistribution. VIP, PV and SST neurons differ significantly from one another in their locomotion coupling Quotation withheld because this record is not cleared for redistribution. SST neurons are suppressed by locomotion Quotation withheld because this record is not cleared for redistribution. nicotinic antagonists dramatically reduced VIP responses to locomotion without blocking nearby non-VIP visual responses Quotation withheld because this record is not cleared for redistribution. the nucleus of the diagonal band is a prominent monosynaptic input to upper-layer V1 VIP neurons Quotation withheld because this record is not cleared for redistribution. at most very sparse direct input from motor cortex was found Quotation withheld because this record is not cleared for redistribution. optogenetic VIP activation in stationary mice raised visual responses by about a third without changing selectivity Quotation withheld because this record is not cleared for redistribution. photolytic damage to VIP cells cut the locomotion enhancement from 86% to 12% Quotation withheld because this record is not cleared for redistribution. VIP activation in anaesthetised mice does not change visual responses, as the circuit predicts Quotation withheld because this record is not cleared for redistribution. locomotion modulation index locomotion modulation index Quotation withheld because this record is not cleared for redistribution. running state running state Quotation withheld because this record is not cleared for redistribution. central rather than peripheral central rather than peripheral Quotation withheld because this record is not cleared for redistribution. behavioral state behavioral state Quotation withheld because this record is not cleared for redistribution. orientation selectivity index (OSI) orientation selectivity index (OSI) Quotation withheld because this record is not cleared for redistribution. running speed running speed Quotation withheld because this record is not cleared for redistribution. locomotion modulation index locomotion modulation index Quotation withheld because this record is not cleared for redistribution. orientation selectivity index orientation selectivity index Quotation withheld because this record is not cleared for redistribution. 37±7% — Average increase in the calcium response of imaged V1 neurons during running, replicating the electrophysiological locomotion effect Quotation withheld because this record is not cleared for redistribution. 0.47±0.03, n=28 — Mean zero-lag cross-correlation between VIP-neuron calcium signal and running speed in darkness Quotation withheld because this record is not cleared for redistribution. 20/28 versus 3/77 — VIP neurons versus non-VIP neurons whose zero-lag correlation with locomotion exceeded 0.4 Quotation withheld because this record is not cleared for redistribution. 0.58±0.03 (n=21), 0.30±0.06 (n=40), −0.19±0.05 (n=11) — Zero-lag locomotion cross-correlations for VIP, PV and SST neurons respectively Quotation withheld because this record is not cleared for redistribution. 155.0±34.8% — Average increase in the GCaMP6 signal of VIP neurons aligned to the start of running events Quotation withheld because this record is not cleared for redistribution. 32.4±8.3%, n=19, p <0.02 — Increase in the visual response of layer 2/3 neurons produced by optogenetic activation of VIP neurons in stationary mice Quotation withheld because this record is not cleared for redistribution. 86±16% versus 12±6% — Locomotion-induced enhancement of non-VIP neuron activity before versus after photolytic damage of nearby VIP neurons Quotation withheld because this record is not cleared for redistribution. 12.41±0.98mV vs. 2.61±0.26mV — Acetylcholine-induced depolarisation of VIP neurons in slices before versus after nicotinic receptor blockade under TTX Quotation withheld because this record is not cleared for redistribution. 37 plus or minus 7% increase in calcium response with running — reproduction of the electrophysiological effect by imaging Quotation withheld because this record is not cleared for redistribution. VIP 0.58 plus or minus 0.03, PV 0.30 plus or minus 0.06, SST -0.19 plus or minus 0.05 — zero-time cross-correlation with locomotion by cell type Quotation withheld because this record is not cleared for redistribution. 20/28 VIP versus 3/77 non-VIP neurons above 0.4 correlation — how specific the locomotion response is to VIP cells Quotation withheld because this record is not cleared for redistribution. 32.4 plus or minus 8.3% — increase in visual response from optogenetic VIP activation Quotation withheld because this record is not cleared for redistribution. 86 plus or minus 16% before versus 12 plus or minus 6% after photo damage — locomotion enhancement lost when VIP cells are destroyed Quotation withheld because this record is not cleared for redistribution. 0 to 1 neurons per mouse in motor cortex against more than 50 labelled VIP neurons — the near-absence of direct motor input Quotation withheld because this record is not cleared for redistribution.

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