The role of corticothalamic circuits in avoidance learning

Avoidance learning entails linking a threat-predictive stimulus (CS) to aversive outcomes (US) and developing a behavioural strategy (shuttling) to forestall harm. This multifactorial process necessitates neural circuits capable of prioritising relevant sensory cues and promoting optimal actions. Auditory cortex (AC) and thalamic reticular nucleus (TRN) send excitatory and inhibitory afferents to auditory thalamus (medial geniculate body; MGB), respectively, and MGB neurons play an active role in associative fear learning. However, it is unclear how AC-MGB and TRN-MGB projections channel information to guide stimulus-outcome associations and behavioural strategy during avoidance learning. To better understand the role of AC-MGB and TRN-MGB projections, I recorded their activity during a 5-day avoidance learning paradigm using genetically restricted calcium indicators and in vivo fibre photometry. I found that AC-MGB projections primarily provide stable sensory representations by encoding aversive cues and auditory cue familiarity. In contrast, inhibitory TRN-MGB projections represented escape decisions and tracked learning-related variables that develop across trials, such as CS value and prediction error. Further downstream, MGB sends projections to medium spiny neurons (MSNs) in tail of striatum (TS), a region that receives dense auditory input and has been implicated in threat prediction. Using optogenetics-assisted circuit mapping in ex vivo slices, I found that thalamostriatal projections from MGB modulated action potential firing in TS MSNs. This regulation of striatal output proceeded in part through a newly identified long-range inhibitory projection from MGB that triggered slow, GABAB-receptor mediated currents in TS MSNs. Though the in vivo relevance of MGB-TS projections remains to be studied, thalamic tuning of striatal output is likely implicated in avoidance learning. Altogether, cortico-thalamo-striatal circuits surrounding MGB exhibit distinct signalling modes and dynamic encoding properties that guide avoidance learning.