Cell-type specific regulation of auditory decision-making

Maharjan, D. M. (April 2024) Cell-type specific regulation of auditory decision-making. PhD thesis, Cold Spring Harbor Laboratory.

	PDF Maharjan_Dennis_SBS_Thesis_Submission_Agreement_2024.pdf Restricted to Repository staff only Download (131kB)
	PDF Maharjan_Dennis_SBS_Thesis_Apr2024.pdf Restricted to Repository staff only until 25 March 2026. Download (39MB)

Abstract

The ability of animals to execute appropriate actions upon sensing changes in their environment can determine whether an animal survives in the wild. The neural correlates of sensorimotor decisions have been extensively studied by scientists across many modalities and multiple species of animals. In this thesis, I will present our investigation of how sensorimotor associations are represented in the brain by training rodents to perform an auditory discrimination task, called the "cloud of tones" task. This task examines the ability of rodents to integrate auditory information and use it to make appropriate motor responses to obtain reward. Mice are trained to make rightward or leftward movements in response to the frequency content of the auditory stimuli presented to them. Our laboratory's prior research has revealed that observed synaptic strengthening patterns in the auditory striatum can be used to predict the sensorimotor associations learned by animals. Given the stria tum' s composition of Drdla (Dl) and Drd2a (D2) expressing medium spiny neurons, we investigated the roles these neuronal cell types play in regulating auditory decision-making. Artificially modulating the activity of these two cell-types in the auditory striatum revealed opposing behavioral effects during task performance. Optogenetically activating Dl neurons led to a robust bias in the behavior of the animals to making contralateral decisions, decisions opposite to the hemisphere of the brain being stimulated. Whereas, activating D2 neurons led to a strong bias in the ipsilateral direction, decisions in the same side as the hemisphere being stimulated. GCaMP8f activity of these cell-types was recorded using fiber photometry, which revealed that D1 neurons were highly active during task performance whereas, D2 neurons were relatively inactive. D1 activity increased based on the frequency content of the stimulus presented as well as the initiation of contralateral movements during decision-making. Taken together, these results indicate that even though D1 and D2 neural networks in the auditory striatum are organized to induce opposing effects, D1 neurons are largely recruited to regulate auditory decision-making behavior.

Item Type:	Thesis (PhD)
Subjects:	organism description > animal behavior organism description > animal behavior > auditory
CSHL Authors:	Maharjan, Dennis
Communities:	CSHL labs > Zador lab School of Biological Sciences > Theses
Depositing User:	Kathleen McGuire
Date:	8 April 2024
Date Deposited:	25 Mar 2025 16:08
Last Modified:	25 Mar 2025 16:08
URI:	https://repository.cshl.edu/id/eprint/41834

Actions (login required)

Administrator's edit/view item