<p class="first" id="d10317352e144">The neuromodulator acetylcholine (ACh) is crucial
for several cognitive functions,
such as perception, attention, and learning and memory. Whereas, in most cases, the
cellular circuits or the specific neurons via which ACh exerts its cognitive effects
remain unknown, it is known that auditory cortex (AC) neurons projecting from layer
5B (L5B) to the inferior colliculus, corticocollicular neurons, are required for cholinergic-mediated
relearning of sound localization after occlusion of one ear. Therefore, elucidation
of the effects of ACh on the excitability of corticocollicular neurons will bridge
the cell-specific and cognitive properties of ACh. Because AC L5B contains another
class of neurons that project to the contralateral cortex, corticocallosal neurons,
to identify the cell-specific mechanisms that enable corticocollicular neurons to
participate in sound localization relearning, we investigated the effects of ACh release
on both L5B corticocallosal and corticocollicular neurons. Using
<i>in vitro</i> electrophysiology and optogenetics in mouse brain slices, we found
that ACh generated
nicotinic ACh receptor (nAChR)-mediated depolarizing potentials and muscarinic ACh
receptor (mAChR)-mediated hyperpolarizing potentials in AC L5B corticocallosal neurons.
In corticocollicular neurons, ACh release also generated nAChR-mediated depolarizing
potentials. However, in contrast to the mAChR-mediated hyperpolarizing potentials
in corticocallosal neurons, ACh generated prolonged mAChR-mediated depolarizing potentials
in corticocollicular neurons. These prolonged depolarizing potentials generated persistent
firing in corticocollicular neurons, whereas corticocallosal neurons lacking mAChR-mediated
depolarizing potentials did not show persistent firing. We propose that ACh-mediated
persistent firing in corticocollicular neurons may represent a critical mechanism
required for learning-induced plasticity in AC.
</p><p id="d10317352e149">
<b>SIGNIFICANCE STATEMENT</b> Acetylcholine (ACh) is crucial for cognitive functions.
Whereas in most cases the
cellular circuits or the specific neurons via which ACh exerts its cognitive effects
remain unknown, it is known that auditory cortex (AC) corticocollicular neurons projecting
from layer 5B to the inferior colliculus are required for cholinergic-mediated relearning
of sound localization after occlusion of one ear. Therefore, elucidation of the effects
of ACh on the excitability of corticocollicular neurons will bridge the cell-specific
and cognitive properties of ACh. Our results suggest that cell-specific ACh-mediated
persistent firing in corticocollicular neurons may represent a critical mechanism
required for learning-induced plasticity in AC. Moreover, our results provide synaptic
mechanisms via which ACh may mediate its effects on AC receptive fields.
</p>