# Multiscale analysis of how the basal ganglia impact cortical processing in behaving mice

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $475,277

## Abstract

Project Summary/Abstract
The overall goal of this project is to determine how output from the basal ganglia influences cerebral cortical
activity in the processes of decision making, motor planning, and movement execution. The studies will employ
mice as the best suited species in order to bring modern optogenetic and genetically encoded sensor
technologies to bear on this critical gap in our understanding of brain function. In aim 1 we address the impact
of basal ganglia output on network activity in cortex across sensory and motor areas. To this end will use
genetically encoded calcium sensors selectively expressed in thalamic neurons receiving input from the basal
ganglia (BGT) to record the pattern of activation of these thalamic axons in cortex with wide-field imaging. We
will further image the resulting activation or inhibition of these thalamic terminals in cortex upon optogenetic
manipulations of basal ganglia output activity in quietly awake mice and mice performing a forced choice
left/right licking task. In a second study under aim 1 we will use genetically encoded voltage sensors to image
the postsynaptic activation of specific cortical cell types upon optogenetic basal ganglia output manipulations.
The expected outcome of these studies is that we will have characterized the impact of basal ganglia
modulated thalamic activity on cortical network activation. In aim 2 we will address the question of how these
network effects are mechanistically achieved at the cellular and subcellular level. We hypothesize that the input
of BGT, which is primarily restricted to superficial cortical layers, will result in the activation of non-linear
dendritic properties of pyramidal cell dendrites such as calcium or NMDA spikes. To address this hypothesis
we will use simultaneous 2-photon calcium imaging in thalamic terminals and cortical dendrites in the context
of our behavioral task. In a second study we will use whole cell recordings in behaving mice in conjunction with
optogenetic basal ganglia output manipulations to determine the balance of excitatory and inhibitory effects
converging on pyramidal cells as a consequence of basal ganglia activity. Finally, in aim 3 of our proposed
research we will use detailed biophysical neural modeling to construct a thalamo-cortical network model that
can replicate the observed physiological responses to basal ganglia output manipulations. On the subcellular
level, we will use this model to determine the specific synaptic input strengths and voltage-gated ion channel
types in pyramidal neuron dendrites that are required to explain observed responses. On the network level we
will use the model to search through a large number of optogenetic basal ganglia output manipulations to
identify candidate stimulus patterns that indicate specific mechanisms at work. We will then employ these
patterns in our recordings to test model predictions and come to a better understanding of network interactions
resulting from basal...

## Key facts

- **NIH application ID:** 9952430
- **Project number:** 5R01NS111470-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** DIETER JAEGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $475,277
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952430

## Citation

> US National Institutes of Health, RePORTER application 9952430, Multiscale analysis of how the basal ganglia impact cortical processing in behaving mice (5R01NS111470-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952430. Licensed CC0.

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