In awake rodents, the neural representation of olfactory information in the olfactory bulb is largely dependent on brain state and behavioral context. Learning-modified neural plasticity has been observed in mitral/tufted cells, the main output neurons of the olfactory bulb. Here, we propose that the odor information encoded by mitral/tufted cell responses in awake mice is highly dependent on the behavioral task demands. We used fiber photometry to record calcium signals from the mitral/tufted cell population in awake, head-fixed male mice under different task demands. We found that the mitral/tufted cell population showed similar responses to two distinct odors when the odors were presented in the context of a go/go task, in which the mice received a water reward regardless of the identity of the odor presented. However, when the same odors were presented in a go/no-go task, in which one odor was rewarded and the other was not, then the mitral cell population responded very differently to the two odors, characterized by a robust reduction in the response to the nonrewarded odor. Thus, the representation of odors in the mitral/tufted cell population depends on whether the task requires discrimination of the odors. Strikingly, downstream of the olfactory bulb, pyramidal neurons in the posterior piriform cortex also displayed a task-demand-dependent neural representation of odors, but the anterior piriform cortex did not, indicating that these two important higher olfactory centers use different strategies for neural representation.

No abstract

Genetically distinct GABAergic interneuron subtypes play diverse roles in cortical circuits. Previous studies revealed that microRNAs (miRNAs) are differentially expressed in cortical interneuron subtypes, and are essential for the normal migration, maturation, and survival of medial ganglionic eminence-derived interneuron subtypes. How miRNAs function in vasoactive intestinal peptide expressing (VIP+) interneurons derived from the caudal ganglionic eminence remains elusive. Here, we conditionally removed Dicer in postmitotic VIP+ interneurons to block miRNA biogenesis. We found that the intrinsic and synaptic properties of VIP+ interneurons and pyramidal neurons were concordantly affected prior to a progressive loss of VIP+ interneurons. In vivo recording further revealed elevated cortical local field potential power. Mutant mice had a shorter life span but exhibited better spatial working memory and motor coordination. Our results demonstrate that miRNAs are indispensable for the function and survival of VIP+ interneurons, and highlight a key role of VIP+ interneurons in cortical circuits.

Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα+ neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+ neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1f/f mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobePCs → FNCaMKIIα+ circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

Aim: MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP + ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP + interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP + miRNA affects olfactory