Distinct mechanisms of CB1 and GABA<sub>B</sub> receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus

Sitzia, Giacomo; Abrahao, Karina Possa; Liput, Daniel J.; Calandra, Gian Marco; Lovinger, David M.

doi:10.1113/jp283614

Cited by 3 publications

References 48 publications

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A non-canonical striatopallidal Go pathway that supports motor control

Labouesse,

Torres-Herraez,

Chohan

et al. 2023

Nat Commun

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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 axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe 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 Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.

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A non-canonical striatopallidal Go pathway that supports motor control

Labouesse,

Torres-Herraez,

Chohan

et al. 2023

Nat Commun

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Spontaneous Activity of the Local GABAergic Synaptic Network Causes Irregular Neuronal Firing in the External Globus Pallidus

et al. 2023

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Autonomously firing GABAergic neurons in the external globus pallidus (GPe) form a local synaptic network. In slices, most GPe neurons receive a continuous inhibitory synaptic barrage from 1-2 presynaptic GPe neurons. We measured the barrage's effect on the firing rate and regularity of GPe neurons in male and female mice using perforated patch recordings. Silencing the firing of parvalbumin-positive (PV+) GPe neurons by activating genetically expressed Archaerhodopsin current increased the firing rate and regularity of PV- neurons. In contrast, silencing Npas1+ GPe neurons with Archaerhodopsin had insignificant effects on Npas1- neuron firing. Blocking spontaneous GABAergic synaptic input with gabazine reproduced the effects of silencing PV+ neuron firing on the firing rate and regularity of Npas1+ neurons and had similar effects on PV+ neuron firing. To simulate the barrage, we constructed conductance waveforms for dynamic clamp based on experimentally measured inhibitory postsynaptic conductance trains from 1-2 unitary local connections. The resulting inhibition replicated the effect on firing seen in the intact active network in the slice. We then increased the number of unitary inputs to match estimates of local network connectivityin vivo. As few as 5 unitary inputs produced large increases in firing irregularity. The firing rate was also reduced initially, but PV+ neurons exhibited a slow spike frequency adaptation that partially restored the rate despite sustained inhibition. We conclude that the irregular firing pattern of GPe neuronsin vivois largely due the ongoing local inhibitory synaptic barrage produced by the spontaneous firing of other GPe neurons.SIGNIFICANCE:Functional roles of local axon collaterals in the external globus pallidus (GPe) have remained elusive due to difficulty in isolating local inhibition from other GABAergic inputsin vivo, and in preserving the autonomous firing of GPe neurons and detecting their spontaneous local inputs in slices. We used perforated patch recordings to detect spontaneous local inputs during rhythmic firing. We found that the autonomous firing of single presynaptic GPe neurons produces inhibitory synaptic barrages that significantly alter the firing regularity of other GPe neurons. Our findings suggest that although GPe neurons receive input from only a few other GPe neurons, each local connection has a large impact on their firing.

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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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Distinct mechanisms of CB1 and GABA_B receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus

Cited by 3 publications

References 48 publications

A non-canonical striatopallidal Go pathway that supports motor control

A non-canonical striatopallidal Go pathway that supports motor control

Spontaneous Activity of the Local GABAergic Synaptic Network Causes Irregular Neuronal Firing in the External Globus Pallidus

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

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Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus

Cited by 3 publications

References 48 publications

A non-canonical striatopallidal Go pathway that supports motor control

A non-canonical striatopallidal Go pathway that supports motor control

Spontaneous Activity of the Local GABAergic Synaptic Network Causes Irregular Neuronal Firing in the External Globus Pallidus

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

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Distinct mechanisms of CB1 and GABA_B receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus