Cholinergic boutons are closely associated with excitatory cells and four subtypes of inhibitory cells in the inferior colliculus

Beebe, Nichole L.; Schofield, Brett R.

doi:10.1016/j.jchemneu.2021.101998

Cited by 12 publications

(9 citation statements)

References 91 publications

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“…The IC receives cholinergic input from the two nuclei that comprise the PMT: the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus. Together, these nuclei distribute cholinergic axons and synapses throughout the IC, contacting both GABAergic and glutamatergic neurons (Motts and Schofield, 2009;Schofield et al, 2011;Noftz et al, 2020;Beebe and Schofield, 2021). However, the specific neuronal populations that cholinergic terminals synapse onto in the IC remain unclear.…”

Section: Cholinergic Synapses Are Found Adjacent To the Somas And Dendrites Of Vip Neuronsmentioning

confidence: 99%

α3β4∗ Nicotinic Acetylcholine Receptors Strongly Modulate the Excitability of VIP Neurons in the Mouse Inferior Colliculus

Rivera-Perez

Kwapiszewski

Roberts

2021

Front. Neural Circuits

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The inferior colliculus (IC), the midbrain hub of the central auditory system, receives extensive cholinergic input from the pontomesencephalic tegmentum. Activation of nicotinic acetylcholine receptors (nAChRs) in the IC can alter acoustic processing and enhance auditory task performance. However, how nAChRs affect the excitability of specific classes of IC neurons remains unknown. Recently, we identified vasoactive intestinal peptide (VIP) neurons as a distinct class of glutamatergic principal neurons in the IC. Here, in experiments using male and female mice, we show that cholinergic terminals are routinely located adjacent to the somas and dendrites of VIP neurons. Using whole-cell electrophysiology in brain slices, we found that acetylcholine drives surprisingly strong and long-lasting excitation and inward currents in VIP neurons. This excitation was unaffected by the muscarinic receptor antagonist atropine. Application of nAChR antagonists revealed that acetylcholine excites VIP neurons mainly via activation of α3β4∗ nAChRs, a nAChR subtype that is rare in the brain. Furthermore, we show that acetylcholine excites VIP neurons directly and does not require intermediate activation of presynaptic inputs that might express nAChRs. Lastly, we found that low frequency trains of acetylcholine puffs elicited temporal summation in VIP neurons, suggesting that in vivo-like patterns of cholinergic input can reshape activity for prolonged periods. These results reveal the first cellular mechanisms of nAChR regulation in the IC, identify a functional role for α3β4∗ nAChRs in the auditory system, and suggest that cholinergic input can potently influence auditory processing by increasing excitability in VIP neurons and their postsynaptic targets.

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Section: Cholinergic Synapses Are Found Adjacent To the Somas And Dendrites Of Vip Neuronsmentioning

confidence: 99%

α3β4∗ Nicotinic Acetylcholine Receptors Strongly Modulate the Excitability of VIP Neurons in the Mouse Inferior Colliculus

Rivera-Perez

Kwapiszewski

Roberts

2021

Front. Neural Circuits

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“…Using a Western blot analysis on mouse brain tissue, this antibody selectively bound a set of closely associated protein isoforms of NeuN, a neuron-specific protein which binds to DNA in neurons. Several studies have used this antibody as a general neuronal marker in the IC (Mellott et al, 2014 ; Beebe et al, 2016 ; Goyer et al, 2019 ; Silveira et al, 2020 ; Beebe and Schofield, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…These sections were immunolabeled for GAD67 and GlyT2 and imaged using the 20× objective of a Leica TCS SP8 confocal microscope. The pattern of GAD67 and GlyT2 immunolabeling has previously been used to identify IC subdivisions (Buentello et al, 2015 ; Silveira et al, 2020 ; Beebe and Schofield, 2021 ). For each RB injection case, IC subdivision boundaries were drawn based on the distribution of GABA and glycinergic terminals in the most similar reference sections.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory NPY Neurons Provide a Large and Heterotopic Commissural Projection in the Inferior Colliculus

Anair

Silveira

Mirjalili

et al. 2022

Front. Neural Circuits

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Located in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The right and left sides of the IC are interconnected by a dense fiber tract, the commissure of the IC (CoIC), that provides each IC with one of its largest sources of input (i.e., the contralateral IC). Despite its prominence, the CoIC remains poorly understood. Previous studies using anterograde and retrograde tract-tracing showed that IC commissural projections are predominately homotopic and tonotopic, targeting mirror-image locations in the same frequency region in the contralateral IC. However, it is unknown whether specific classes of neurons, particularly inhibitory neurons which constitute ~10%–40% of the commissural projection, follow this pattern. We, therefore, examined the commissural projections of Neuropeptide Y (NPY) neurons, the first molecularly identifiable class of GABAergic neurons in the IC. Using retrograde tracing with Retrobeads (RB) in NPY-hrGFP mice of both sexes, we found that NPY neurons comprise ~11% of the commissural projection. Moreover, focal injections of Retrobeads showed that NPY neurons in the central nucleus of the IC exhibit a more divergent and heterotopic commissural projection pattern than non-NPY neurons. Thus, commissural NPY neurons are positioned to provide lateral inhibition to the contralateral IC. Through this circuit, sounds that drive activity in limited regions on one side of the IC likely suppress activity across a broader region in the contralateral IC.

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“…Using a Western blot analysis on mouse brain tissue, this antibody showed to selectively bind a set of closely associated protein isoforms of NeuN, a neuron specific protein which binds to DNA in neurons. Several studies have used this antibody as a general neuronal marker in the IC (Mellott et al, 2014; Beebe et al, 2016; Goyer et al, 2019; Silveira et al, 2020; Beebe and Schofield, 2021).…”

Section: Methodsmentioning

confidence: 99%

“…These sections were immunolabeled for GAD67 and GlyT2 and imaged using the 20x objective of a Leica TCS SP8 confocal microscope. The pattern of GAD67 and GlyT2 immunolabeling has previously been used to identify IC subdivisions (Buentello et al, 2015; Silveira et al, 2020; Beebe and Schofield, 2021). For each RB injection case, IC subdivision boundaries were drawn based on the distribution of GABA and glycinergic terminals in the most similar reference sections.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory NPY neurons provide a large and heterotopic commissural projection in the inferior colliculus

Anair

Silveira

Mirjalili

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Located in the midbrain, the inferior colliculus (IC) plays an essential role in many auditory computations, including speech processing and sound localization. The right and left side of the IC are interconnected by a dense fiber tract, the commissure of the IC (CoIC), that provides each IC with one its largest sources of input (i.e., the contralateral IC). Despite its prominence, the CoIC remains poorly understood. Previous studies using anterograde and retrograde tract-tracing showed that IC commissural projections are predominately homotopic and tonotopic, targeting mirror-image locations in the same frequency region in the contralateral IC. However, it is unknown whether specific classes of neurons, particularly inhibitory neurons which constitute ~10-40% of the commissural projection, follow this pattern. We therefore examined the commissural projections of Neuropeptide Y (NPY) neurons, the first molecularly identifiable class of GABAergic neurons in the IC. Using retrograde tracing with Retrobeads in NPY-hrGFP mice of both sexes, we found that NPY neurons comprise ~11% of the commissural projection. Moreover, focal injections of Retrobeads showed that NPY neurons in the central nucleus of the IC exhibit a more divergent and heterotopic commissural projection pattern than non-NPY neurons. Thus, commissural NPY neurons are positioned to provide cross-frequency, lateral inhibition to the contralateral IC. Through this circuit, sounds that drive activity in limited frequency bands on one side of the IC might suppress activity across a larger number of frequency bands in the contralateral IC.

show abstract

Cholinergic boutons are closely associated with excitatory cells and four subtypes of inhibitory cells in the inferior colliculus

Cited by 12 publications

References 91 publications

α3β4∗ Nicotinic Acetylcholine Receptors Strongly Modulate the Excitability of VIP Neurons in the Mouse Inferior Colliculus

α3β4∗ Nicotinic Acetylcholine Receptors Strongly Modulate the Excitability of VIP Neurons in the Mouse Inferior Colliculus

Inhibitory NPY Neurons Provide a Large and Heterotopic Commissural Projection in the Inferior Colliculus

Inhibitory NPY neurons provide a large and heterotopic commissural projection in the inferior colliculus

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