Physiological and behavioural relevance of the cerebellar-periaqueductal grey pathway in fear responses

Abstract

The cerebellum has been recognised to be involved in emotional behaviour, although
its exact role remains to be determined. In this work I investigate its
relationship with an important hub within the fear network, the periaqueductal
grey.
Using a combination of anatomical, electrophysiological, behavioural, and computational
techniques in rats I have explored the role of the medial cerebellar nucleus
(mCN) to ventrolateral periaqueductal grey (vlPAG) pathway in the context of fear
conditioning.
Anatomical tracer studies using both anterograde and retrograde viruses have
mapped a direct (monosynaptic) projection from mCN to the vlPAG. This was
physiologically confirmed by recording short latency field potential responses in
the vlPAG elicited by electrical stimulation of the mCN. Inhibition of this pathway,
using DREADDs during an auditory fear conditioning paradigm, reduced ultrasonic
vocalizations (USVs) and slowed the rate of fear extinction, suggesting that
mCN-vlPAG pathway modulates multiple aspects of fear-related responses. To further
study the role of these brain areas in fear extinction processes, event related
potentials (ERPs) recorded in the mCN and vlPAG were investigated: both brain
structures respond to the onset and offset of the conditioned stimulus during extinction,
with the offset response decreasing from early to late trials. Application
of dynamic causal modelling (DCM) to the ERP data showed that strong coupling
of the mCN-vlPAG pathway promotes fear extinction.
Taken all together these findings indicate that the mCN, through direct projections
to the vlPAG, is able to modulate fear extinction and other fear conditioned
behaviours.

Date of Award	24 Jun 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Rosalyn Moran (Supervisor), Bridget Lumb (Supervisor) & Richard Apps (Supervisor)