Macquarie University
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Inhibitory control of motor and respiratory components of orienting responses by the substantia nigra pars reticulata

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posted on 2022-11-10, 00:40 authored by Stephanie Kennett

The ability to generate appropriate responses to environmental stimuli is a strong driver of natural selection. The superior colliculus (SC), a highly conserved midbrain structure, plays an integral role in coordinating responses to environmental cues by integrating multiple sensory inputs and coordinating both behavioural (such orienting and escape) and physiological responses (such as changes to respiration, blood pressure, and heart rate). However, the SC receives tonic inhibition that acts as a brake to its excitability, reducing unnecessary responses. It is currently unknown where this tonic GABA (𝛾-aminobutyric acid) drive originates. A likely candidate is the substantia nigra pars reticulata (SNr). We aimed to confirm that the SNr is a major source of GABA input to the SC.  We selectively targeted SNr GABAergic cells with a fluorescent viral tracer to confirm a GABAergic SNr-SC pathway in rats, and to survey other regions for potential receipt of SNr GABAergic input as it was difficult to target solely the SNr-SC pathway alone. We then targeted SNr GABAergic neurons with inhibitory optogenetics to elucidate their role in mediating SC-evoked responses. SNr GABAergic function was analysed during deep and light anaesthesia, sleep and awake, focusing on rat orienting behaviour, respiration, and blood pressure.  We report that SNr GABAergic neurons send extensive projections to both the intermediate and deep layers of the SC, whilst also projecting to the motor nuclei in the ventromedial, paracentral and centrolateral regions of the thalamus. Inhibition of the SNr elicits robust head and body orienting response to the contralateral side when unilaterally inhibited and to both sides when bilaterally inhibited in freely behaving rats. Bilaterally SNr inhibition also elicited an increase in respiration in awake rats. However, under light and deep anaesthesia and in natural sleep, we saw no response from bilateral SNr GABA inhibition. Under deep anaesthesia there was no change to phrenic nerve activity, sympathetic nerve activity or blood pressure, even when SNr inhibition was conducted at the same as sensory stimuli (looming, clapping, whisking, and pinching). These responses are likely to be coordinated through the connection to the SC, as results are synonymous with SC activation studies, although difficult to conclude as all SNr projections were inhibited. As such, we suggest a state-dependency in the SNr GABAergic neurons, where SNr inhibition to downstream brain regions (including the SC) is high during wake and disinhibited to create behavioural and respiratory changes, and SNr inhibition is reduced or removed during sleep and under anaesthesia.


Table of Contents

Introduction -- Methods -- Results -- Discussion -- References


A thesis submitted for the partial fulfilment of the requirements of the degree of Master of Research

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


Thesis (MRes), Macquarie University, Faculty of Medicine, Health and Human Sciences, Department of Biomedical Sciences, 2021

Department, Centre or School

Department of Biomedical Sciences

Year of Award


Principal Supervisor

Simon McMullan

Additional Supervisor 1

Anita Turner

Additional Supervisor 2

Peter Burke


Copyright: The Author Copyright disclaimer:




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