# Neuron heterogeneity and network dynamic control of synaptic responses in the external globus pallidus

> **NIH NIH F31** · UNIVERSITY OF TEXAS SAN ANTONIO · 2022 · $37,952

## Abstract

Project Summary/Abstract
 The external globus pallidus (GPe) is traditionally viewed as a homogenous relay nucleus in the movement-
suppressing indirect pathway but is now known to be more complex. Indirect pathway striatopallidal neurons
provide transient inhibition to GPe neurons expressing Parvalbumin (PV), but direct pathway striatal neurons
also inhibit the GPe, targeting primarily Npas1 neurons. PV and Npas1 neurons have different downstream
targets and are interconnected by a network of local axon collaterals. In addition, both cell groups exhibit
intrinsic oscillations and fire rapidly, even in brain slices. In healthy animals, GPe neurons exhibit little to no
spike-time correlations, which emerge in Parkinsonian states and could be attributed to local connectivity or
common striatopallidal input. The goal of this proposal is to investigate the mechanisms by which the local
collateral network in the GPe (1) shapes the spontaneous pattern of GPe neuron firing in the absence of
striatal input, and (2) controls the spiking responses of GPe neurons to synaptic input from direct and
indirect pathway striato-pallidal neurons. To address these questions, this proposal is divided into two aims.
(Aim 1) Determine how the GPe network forms its own pattern of firing. Synaptic potentials from local axon
collaterals and their effect on the firing patterns of PV and Npas1 neurons will be measured in slice
preparations using perforated patch-clamp recordings before and after blocking synaptic transmission in local
collaterals with GABA receptor antagonists. The spiking dynamics of PV and Npas1 neurons can be
summarized in the dynamics of their oscillation phase. Using a phase resetting model, the effect of simulated
local IPSP barrages on the phase dynamics of PV and Npas1 neurons will be determined, providing a
mechanism for their influence on firing patterns. (Aim 2) Determine how the GPe networks shape spiking
responses to striato-pallidal inputs. Indirect pathway signals will be mimicked using a brief Archaerhodopsin
(Arch) activation in PV neurons, and Arch activation in Npas1 neurons will be used to mimic direct pathway
signals. The spiking responses of the same cell type (directly inhibited by Arch and indirectly disinhibited by
the local network) and the other cell type (disinhibited by the network only) will be measured. The effect of the
local network on the spiking responses of cells to direct inhibition by Arch will be isolated by subtracting the
measurements repeated in the presence of GABA antagonists. The phase resetting model will be used to
provide a mechanism for how the GPe network shapes spiking responses to striato-pallidal signals. Under this
fellowship, the applicant will continue his training in slice electrophysiology and coding, honing his skills as an
experimentalist and his quantitative approach to research. The applicant will develop a strong mathematical
framework by training under his sponsor and a supporting group of comp...

## Key facts

- **NIH application ID:** 10464917
- **Project number:** 1F31NS127499-01
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** James Jones
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,952
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464917

## Citation

> US National Institutes of Health, RePORTER application 10464917, Neuron heterogeneity and network dynamic control of synaptic responses in the external globus pallidus (1F31NS127499-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464917. Licensed CC0.

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