Fratzl, Alex; (2022) Flexible inhibitory control of defensive behaviour by the ventral lateral geniculate nucleus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Animals can react differently to similar sensory information depending on behavioural circumstances and previous experience. This flexibility is thought to depend on neural inhibition, through suppression of inappropriate and disinhibition of appropriate actions. In this thesis, I identified the ventral lateral geniculate nucleus (vLGN), an inhibitory prethalamic area, as a critical node for the control of visually evoked defensive responses in mice. First, I characterised the structural and functional organisation of the vLGN. Then, taking advantage of a well-characterised model for instinctive behavioural decisions – escape from imminent threat – I showed that GABAergic projections from vLGN to the medial superior colliculus (mSC), a known hub for threat-evoked defensive behaviours, convey information about previous experience of threat and assessment of risk in the environment. Activity in these projections was reduced when mice had experienced a threatening stimulus, while it was elevated after mice learned that stimuli did not pose any danger. Consistently, the chemogenetic suppression of vLGN activity increased risk-avoidance behaviour. The optogenetic activation of vLGN abolished escape responses to imminent visual threats, while suppressing vLGN activity increased the escape probability, demonstrating that vLGN exerts strong, bidirectional control over escape responses. Moreover, electrophysiological mSC recordings in vivo during optogenetic stimulation of vLGN, revealed that vLGN specifically suppresses the activity of visually responsive but not auditory-responsive neurons in the mSC. The optogenetic manipulation of GABAergic projections from vLGN to mSC more strongly influenced escape responses to visual than to auditory threats, suggesting a specificity of this pathway for visually guided behaviours. Together, these results indicate that vLGN flexibly controls the threshold for instinctive responses to imminent visual threat, depending on the animal’s prior experience and its anticipation of danger in the environment. These findings significantly strengthen the circuit-level understanding of flexible behaviour, and how different types of information are integrated to inform decisions.

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