Synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers

Kramer, Paul F; Brill-Weil, Samuel G; Cummins, Alex; Zhang, Renshu; Camacho‐Hernandez, Gisela Andrea; Newman, Amy Hauck; Eldridge, Mark; Averbeck, Bruno B.; Khaliq, Zayd M.

doi:10.1016/j.neuron.2022.07.011

Cited by 49 publications

(49 citation statements)

References 75 publications

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“…We also wondered if and to what extent GPe terminals receive a copy of the same neuronal information sent by dSPNs to SNr terminals. Indeed, existing work points to a highly correlated but possible dissociation of activity between soma and presynaptic terminals in various systems [30][31][32][33] and to the existence of multiple mechanisms for local regulation of presynaptic calcium levels 34,35 . In this respect, the degree to which the activity of presynaptic terminals from two different axonal outputs correlates vs. dissociates has not been addressed.…”

Section: Dspns Send Copies Of Motor Signals To the Gpe And Snr Contin...mentioning

confidence: 99%

A non-canonical striatopallidal “Go” pathway that supports motor control

Labouesse

Torres-Herraez

Chohan

et al. 2023

Preprint

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In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess “bridging” collaterals within the globus pallidus (GPe), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches to dissect the roles of bridging collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of pallidostriatal Npas1 neurons. We propose a model by which dSPN GPe collaterals (“striatopallidal Go pathway”) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 signals going back to the striatum.

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Section: Dspns Send Copies Of Motor Signals To the Gpe And Snr Contin...mentioning

confidence: 99%

A non-canonical striatopallidal “Go” pathway that supports motor control

Labouesse

Torres-Herraez

Chohan

et al. 2023

Preprint

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“…Both α4β2* and α7* nAChRs are associated with axo-axonic regulation of the release of many transmitters with studies of glutamate, GABA and dopamine being the most common (Dickinson et al, 2008;Livingstone et al, 2009;Threlfell et al, 2012). Non-α7*nAChRs (α4β2*nAChRs) mediate rapid axonal responses to nicotine (Zhong et al, 2008(Zhong et al, , 2013 in synaptic co-culture preparations as well as in response to ACh release in acute striatal slice (Kramer et al, 2022;Liu et al, 2022). Here we show that although nicotine treatment leads to general FM1-43 de-staining along vHipp axons, closer examination reveals two populations of FM1-43 labeled clusters that are distinguished both by the rate and degree of destaining, and by the proximity of surface α7* nAChRs.…”

Section: Discussionmentioning

confidence: 99%

“…α4β2* and α7* nAChRs are found at pre-synaptic as well as post-/extra-synaptic sites (Jones and Wonnacott, 2004;Zhong et al, 2008;Cheng and Yakel, 2014). Activation of axonal and/or pre-synaptic nAChRs affects the release of many neurotransmitters including glutamate, dopamine, GABA and even ACh (McGehee et al, 1995;Gray et al, 1996;Kramer et al, 2022;Liu et al, 2022). nAChR activity also is linked to synapse development and maturation (Berg and Conroy, 2002;Lozada et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Axonal α7* nicotinic acetylcholine receptors modulate glutamatergic signaling and synaptic vesicle organization in ventral hippocampal projections

Zhong

Akmentin²,

Role³

et al. 2022

Front. Neural Circuits

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Modulation of the release of glutamate by activation of presynaptic nicotinic acetylcholine receptors (nAChRs) is one of the most prevalent mechanism of nicotinic facilitation of glutamatergic transmission in cortico-limbic circuits. By imaging gene chimeric co-cultures from mouse, we examined the role of α7* nAChRs mediated cholinergic modulation of glutamate release and synaptic vesicle organization in ventral hippocampal projections. We directly visualized exogenous and endogenous cholinergic facilitation of glutamate release in this specialized preparation of circuits in vitro. Disrupting α7* nAChRs mediated cholinergic signaling genetically or pharmacologically diminished cholinergic facilitation of glutamate release at presynaptic terminals. Alteration of α7* nAChRs mediated cholinergic signaling along glutamatergic axons also decreased functional synaptic vesicle clustering to presynaptic terminals. These findings suggest that presynaptic α7* nAChRs contribute to cholinergic modulation of glutamate release and synaptic vesicle organization.

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“…(2) Dopamine axons receive input from cholinergic interneurons (Cachope et al, 2012; Threlfell et al, 2012; Zhou et al, 2001), and activation of nicotinic receptors triggers dopamine axon action potential firing (Liu et al, 2022). The structure and organization of this cholinergic input is commonly considered non-synaptic (Chang, 1988; Jones et al, 2001), but recent evidence suggests that functionally, synaptic-like transmission exits (Kramer et al, 2022). Hence, dopamine varicosities may in principle contain postsynaptic scaffolds to tether neurotransmitter receptors, although nicotinic acetylcholine receptors were not enriched in the control dataset.…”

Section: Discussionmentioning

confidence: 99%

Protein composition of axonal dopamine release sites in the striatum

Kershberg

Banerjee

Kaeser

2022

Preprint

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Mechanisms of neuromodulatory transmission in the brain remain ambiguous. Dopamine is a prototypical neuromodulator, and it was recently found that its secretion relies on active zone-like release site assemblies. Here, we use in vivo biotin-identification (iBioID) proximity proteomics in mouse striatum to isolate dopamine release site proteins enriched over the general dopamine axonal protein content. Using three bait proteins, we identified 527 proteins that fall into several synaptic protein classes, including active zone, calcium regulatory and synaptic vesicle proteins. We also detected many proteins not previously associated with synaptic exocytosis. Knockout of the presynaptic organizer protein RIM profoundly disrupted dopamine release site composition assessed by iBioID, while Synaptotagmin-1 knockout did not. Alpha-synuclein, a protein linked to Parkinson's disease, was enriched at release sites, and this enrichment was lost in both tested mutants. We conclude that RIM organizes scaffolded dopamine release sites and we define the protein composition of these sites.

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Synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers

Cited by 49 publications

References 75 publications

A non-canonical striatopallidal “Go” pathway that supports motor control

A non-canonical striatopallidal “Go” pathway that supports motor control

Axonal α7* nicotinic acetylcholine receptors modulate glutamatergic signaling and synaptic vesicle organization in ventral hippocampal projections

Protein composition of axonal dopamine release sites in the striatum

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