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Defiance International

Study type: In vivo/preclinical · Status: Evidence verified by machine against declared source

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

Nature communications · 2019

Study scale: Bottom trace: slow postsynaptic inward current of the L1 interneuron (black trace, average of 57 sweeps), blocked by nAChR antagonists (DHßE 10 µM, grey trace). e Histogram of onset delays of postsynaptic currents relative to the peak amplitude of the electrical stimulation-induced presynaptic AP (from n = 11 connected cell pairs). f Amplitudes of successive unitary synaptic currents in the same ChAT-VIP L1-interneuron cell pair as in (d). g Recordings from the same neuron pair as in (d), but now AP firing was induced by activating ChR2 with a blue-light flash.

Abstract only: Open source record

Product or molecular entity relationships

  • VIP: Exact entity relationship. Legacy citation custody associates this source with the catalog record; no product-relevance conclusion is implied.

Public plain-language summary

The published text is limited to the declared source and preserves reported uncertainty. It does not establish efficacy, safety, suitability, or evidence strength.

Research question

Whether these neurons are a local source of ACh in the prefrontal cortex relevant for attention is not known.

Study design

Laser-ON and laser-OFF trials were assigned randomly in each session (50 ON, 50 OFF). c Accuracy of responding by rats injected either in BF or mPFC (CHAT-VIP), or control littermates that received only AAV5::DIO-EYFP injections [CTRL: n = 9; ChAT-VIP: n = 7; BF: n = 11; two-way ANOVA, effect of interaction light × virus F(2,24) = 5.920; p = 0.0081; Sidak’s correction ChAT-VIP: p = 0.0102 ON vs. OFF; Sidak’s correction BF: p = 0.0030 ON vs. OFF].

Participants or experimental system

Traditionally, it is assumed that neocortical ACh is released exclusively from terminals of axonal projections whose cell bodies reside in basal forebrain (BF) nuclei6,7.

Study scale

Bottom trace: slow postsynaptic inward current of the L1 interneuron (black trace, average of 57 sweeps), blocked by nAChR antagonists (DHßE 10 µM, grey trace). e Histogram of onset delays of postsynaptic currents relative to the peak amplitude of the electrical stimulation-induced presynaptic AP (from n = 11 connected cell pairs). f Amplitudes of successive unitary synaptic currents in the same ChAT-VIP L1-interneuron cell pair as in (d). g Recordings from the same neuron pair as in (d), but now AP firing was induced by activating ChR2 with a blue-light flash.

Intervention or exposure

A fraction (10–20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons.

Comparator

Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs.

Outcomes examined

The neurotransmitter acetylcholine (ACh) shapes activity of cortical neurons and supports cognitive functions such as learning, memory and attention1–3.

Key findings

VIP interneurons have been shown to disinhibit pyramidal neurons by inhibiting other interneuron types.

Limitations and uncertainty

Despite molecular, morphological and physiological characterizations, technical limitations thus far prevented a direct demonstration of whether these ChAT-expressing VIP interneurons release ACh.

Product relevance and evidence boundary

This record is a published study, held here with its citation and review status. It is not a statement that any catalog item is effective, safe, or suitable for any use, and nothing in it is a dose or a protocol.

Evidence verified by machine against declared source. Verification is limited to the declared source and review scope. It does not mean independent replication or establish efficacy, safety, or suitability.