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

• Published in: The Journal of neuroscience Vol. 43; no. 8; pp. 1281 - 1297
• Main Authors: Jones, James A, Higgs, Matthew H, Olivares, Erick, Peña, Jacob, Wilson, Charles J
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 22-02-2023
• Subjects: Animals; Axons; Basic Helix-Loop-Helix Transcription Factors; Brain slice preparation; Female; Firing pattern; GABAergic Neurons; Globus pallidus; Globus Pallidus - physiology; Male; Mice; Nerve Tissue Proteins; Neural networks; Neurons; Parvalbumin; Parvalbumins; Regularity; Waveforms; γ-Aminobutyric acid; autonomous firing; basal ganglia; globus pallidus; oscillations; collateral network; recurrent inhibition
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1969-22.2023

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 or 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 or 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 connectivity
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 neurons
is largely due to the ongoing local inhibitory synaptic barrage produced by the spontaneous firing of other GPe neurons.
Functional roles of local axon collaterals in the external globus pallidus (GPe) have remained elusive because of difficulty in isolating local inhibition from other GABAergic inputs
, 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.