ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection

Abstract

Selective processing of behaviorally relevant sensory inputs against irrelevant ones is a fundamental cognitive function, impairments of which have been implicated in major psychiatric disorders. It is known that the thalamic reticular nucleus (TRN) gates sensory information en route to the cortex, however the underlying mechanisms remain unclear. Here we show in mice that deficiency of Erbb4 gene in somatostatin-expressing TRN neurons markedly altered behaviors dependent on sensory selection. Whereas performance in identifying targets from distractors was improved, the ability to switch attention between conflicting sensory cues was impaired. These behavioral changes were mediated by enhanced cortical drive onto TRN that promotes the TRN-mediated cortical feedback inhibition of thalamic neurons. Our results uncover a previously unknown role of ErbB4 in regulating cortico-TRN-thalamic circuit function. We propose that ErbB4 sets the sensitivity of TRN to cortical inputs at levels that can support sensory selection while allowing behavioral flexibility.

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

“…It is the TRN neurons that project to sensory rather than limbic thalamic nuclei that participate in spindle generation, in the inhibition of sensory processing during sleep and in the augmentation of sensory processing during tasks requiring attention during wake (104). SZ is characterized by deficits in sensory gating (105), attentional modulation, and cortical gamma band oscillations, all of which may depend on the modulation of the flow of information from the thalamus to the neocortex by the TRN (103, 106, 107). Abnormal cortical gamma oscillations in SZ are associated with cognitive deficits and are thought to reflect dysfunction of cortical parvalbumin (PV)-containing GABAergic interneurons (108), which are abnormal in SZ (109).…”

Attentional flexibility in the thalamus: now we're getting SOMwhere

“…In this issue of Nature Neuroscience , Ahrens et al. 1 span genes, circuits and behavior to make a compelling case that the receptor tyrosine kinase ErbB4 is responsible for regulating the sensitivity of the thalamic reticular nucleus (TRN) to cortical inputs. In so doing, ErbB4 expression tunes the balance between attention and behavioral flexibility.…”

“…However, the cell types and signaling molecules in the TRN that participate in this regulation are not well understood. Ahrens et al 1 find that ErbB4 normally acts to reduce the strength of cortical inputs onto the somatostatin-positive (SOM + ) subset of TRN cells. Reducing ErbB4 expression in these cells leads to increased cortico-TRN excitation and divergent behavioral consequences in tasks involving attention.…”

“…Surprisingly, SOM-ErbB4 knockout enhanced performance in this task, suggesting that a loss of ErbB4 leads to an enhancement in feature detection. Ahrens et al 1 then mixed things up a bit in the visual/auditory task by changing the reward payout to only follow the light and not the tone while presenting both auditory and visual cues, which sometimes agreed (were congruent) and sometimes disagreed (were incongruent). For example, in an incongruent trial, the light indicated reward to the left and the tone indicated reward to the right.…”

“…How exactly the thalamus is subdivided into distinct functional compartments is still very much an open question. Undoubtedly, as Ahrens et al 1 have shown, the use of continually advancing genetic, physiological and molecular approaches to deconstruct these newly appreciated TRN subnetworks represents a new frontier in understanding the role of the thalamus in regulating perception and behavior.…”