A team from the University of Bristol’s School of Physiology, Pharmacology and Neuroscience, UK, have discovered a key pathway in the brain which leads to anxious and fearful behaviour such as “freezing.” Anxiety and certain psychological disorders, which affect an estimated 264-million people worldwide, are survival responses elicited by the periaqueductal grey (PAG) region of the brain.

Activity in this region is influenced by the hindbrain or cerebellum – it is part of an extensive survival network within the brain.

Neuroscientists investigating the brain’s PAG area fitted animal models with electrodes to record activity and applied a conditioning task, whereby an auditory tone is paired with a small foot shock, to mimic the formation of a ‘fear memory’ and freezing, a behavioural index of fear. Here, a subset of brain cells increased their responsiveness to the conditioned tone, consistent with encoding a fear memory.

However, when cerebellar output was altered during conditioning, the subsequent timing of fear-related neuronal activity in the PAG region became less precise, and the duration of fear-related freezing behaviour was increased, thus confirming that cerebellar-PAG interactions contribute to fear conditioning processes.

The neuroscientists also noticed that the manipulation of a direct cerebellar-PAG pathway caused impairments in fear conditioned freezing and ultrasonic vocalisations.

“Until now, little was understood about how the cerebellum modulates neuronal activity in other brain regions, especially those related to fear and anxiety,” said research associates Dr. Charlotte Lawrenson and Dr. Elena Paci.

“Importantly, our results show that the cerebellum is part of the brain’s survival network that regulates fear memory processes at multiple timescales and in multiple ways; raising the possibility that dysfunctional interactions in the brain’s cerebellar-survival network may underlie fear-related disorders and comorbidities.”

The study demonstrates how PAG encodes fear memory and provides evidence that the cerebellum is an additional key structure in the list of brain regions that contribute to anxiety and fear. The findings are expected to guide treatment options for fear-evoked coping responses and psychological conditions including post-traumatic stress disorder.

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