A specific olfactory cortico-thalamic pathway contributing to sampling performance during odor reversal learning

Abstract

A growing body of evidence shows that olfactory information is processed within a thalamic nucleus in both rodents and humans. The mediodorsal thalamic nucleus (MDT) receives projections from olfactory cortical areas including the piriform cortex (PCX) and is interconnected with the orbitofrontal cortex (OFC). Using electrophysiology in freely moving rats, we recently demonstrated the representation of olfactory information in the MDT and the dynamics of functional connectivity between the PCX, MDT and OFC. Notably, PCX-MDT coupling is specifically increased during odor sampling of an odor discrimination task. However, whether this increase of coupling is functionally relevant is unknown. To decipher the importance of PCX-MDT coupling during the sampling period, we used optogenetics to specifically inactivate the PCX inputs to MDT during an odor discrimination task and its reversal in rats. We demonstrate that inactivating the PCX inputs to MDT does not affect the performance accuracy of an odor discrimination task and its reversal, however it does impact the rats' sampling duration. Indeed, rats in which PCX inputs to MDT were inactivated during the sampling period display longer sampling duration during the odor reversal learning compared to controls-an effect not observed when inactivating OFC inputs to MDT. We demonstrate a causal link between the PCX inputs to MDT and the odor sampling performance, highlighting the importance of this specific corticothalamic pathway in olfaction.

Validation of Olfactory Network Based on Brain Structural Connectivity and Its Association With Olfactory Test Scores

“…While continuous olfactory stimulation is known to cause desensitisation, this decrease in olfactory responsiveness can be modulated by olfactory attention ( Fallon et al, 2018 ). As such, our findings support that olfactory attention may be partly regulated by the thalamus, which falls within the framework of recent animal studies ( Courtiol, 2019 ) and human functional olfactory studies ( Zhou et al, 2019 ).…”

Mediodorsal thalamus is critical for updating during extra-dimensional shifts but not reversals in the attentional set-shifting task

“…Both the SD and ED subtasks require rapid, within trial learning or updating of choice response strategies. Therefore, impaired SD and ED performance would be consistent with selective deficits in learning observed in other rodent studies after MD perturbations (Chakraborty and Mitchell, 2013, for review; Courtiol et al, 2019; Ferguson et al, 2017; Hunt and Aggleton, 1998; Mitchell and Dalrymple-Alford, 2005; Perry et al, 2021). We also predicted our MD lesion rats may show deficits during reversal subtasks given the reciprocal direct connectivity with the OFC (Groenwegen, 1988; Krettek and Price, 1977; Ray and Price, 1992).…”

“…Other studies also confirm MD lesion rats are impaired in acquisition of an initial task rule (Hunt and Aggleton, 1998). Other rodent studies causing temporary perturbations to the MD also show impaired discrimination learning (Ferguson and Gao, 2018; Courtiol et al, 2019). Thus these results from across species reinforce the notion that MD is not simply mimicking the PFC (DeNicola et al, 2020; Miller et al, 2017; Mitchell et al, 2007; Mitchell and Gaffan 2008; Mitchell et al, 2014).…”

A thalamocortical circuit for updating action-outcome associations

“…The present study does not support the idea that these interactions are important for goal-directed behavior, even in a setup known to engage OFC functions (Parkes et al, 2018). The functional relevance of the OFC-MD connections has been documented in other settings as both MD and OFC neurons were found to code for task-relevant elements in an odor-discrimination task (Courtiol and Wilson, 2016); however, this feature was not affected by inhibition of the corticothalamic pathway (Courtiol et al, 2019). In the primate, disconnecting the MD from the ventrolateral and orbital cortex impairs adaptive decision-making after selective outcome devaluation (Browning et al, 2015).…”