Dataset Information

Distinct Roles and Synergistic Function of Fru^M Isoforms in Drosophila Olfactory Receptor Neurons.

ABSTRACT: Sexual dimorphism in Drosophila courtship circuits requires the male-specific transcription factor fru^M, which is alternatively spliced to encode the Fru^MA, Fru^MB, and Fru^MC isoforms. Most fru^M-positive neurons express multiple variants; however, the functional significance of their co-expression remains undetermined. Do co-expressed isoforms each play unique roles to jointly regulate dimorphism? By focusing on fru^M-positive olfactory receptor neurons (ORNs), here, we show that Fru^MB and Fru^MC are both required for males' age-dependent sensitization to aphrodisiac olfactory cues in a cell-autonomous manner. Interestingly, Fru^MB expression is upregulated with age in Or47b and Ir84a ORNs, and its overexpression mimics the effect of age in elevating olfactory responses. Mechanistically, Fru^MB and Fru^MC synergistically mediate response sensitization through cooperation of their respective downstream effectors, namely, PPK25 and PPK23, which are both required for forming a functional amplification channel in ORNs. Together, these results provide critical mechanistic insight into how co-expressed Fru^M isoforms jointly coordinate dimorphic neurophysiology.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7845487 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Distinct Roles and Synergistic Function of FruM Isoforms in Drosophila Olfactory Receptor Neurons.

Zhang Ye Y Ng Renny R Neville Megan C MC Goodwin Stephen F SF Goodwin Stephen F SF Su Chih-Ying CY

Cell reports 20201201 11

Sexual dimorphism in Drosophila courtship circuits requires the male-specific transcription factor fruM, which is alternatively spliced to encode the FruMA, FruMB, and FruMC isoforms. Most fruM-positive neurons express multiple variants; however, the functional significance of their co-expression remains undetermined. Do co-expressed isoforms each play unique roles to jointly regulate dimorphism? By focusing on fruM-positive olfac ...[more]

PMID: 33326795

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Project description:The external globus pallidus (GPe) is a critical node within the basal ganglia circuit. Phasic changes in the activity of GPe neurons during movement and their alterations in Parkinson's disease (PD) argue that the GPe is important in motor control. Parvalbumin-positive (PV+) neurons and Npas1+ neurons are the two principal neuron classes in the GPe. The distinct electrophysiological properties and axonal projection patterns argue that these two neuron classes serve different roles in regulating motor output. However, the causal relationship between GPe neuron classes and movement remains to be established. Here, by using optogenetic approaches in mice (both males and females), we showed that PV+ neurons and Npas1+ neurons promoted and suppressed locomotion, respectively. Moreover, PV+ neurons and Npas1+ neurons are under different synaptic influences from the subthalamic nucleus (STN). Additionally, we found a selective weakening of STN inputs to PV+ neurons in the chronic 6-hydroxydopamine lesion model of PD. This finding reinforces the idea that the reciprocally connected GPe-STN network plays a key role in disease symptomatology and thus provides the basis for future circuit-based therapies.SIGNIFICANCE STATEMENT The external pallidum is a key, yet an understudied component of the basal ganglia. Neural activity in the pallidum goes awry in neurologic diseases, such as Parkinson's disease. While this strongly argues that the pallidum plays a critical role in motor control, it has been difficult to establish the causal relationship between pallidal activity and motor function/dysfunction. This was in part because of the cellular complexity of the pallidum. Here, we showed that the two principal neuron types in the pallidum have opposing roles in motor control. In addition, we described the differences in their synaptic influence. Importantly, our research provides new insights into the cellular and circuit mechanisms that explain the hypokinetic features of Parkinson's disease.

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Dataset Information

Distinct Roles and Synergistic Function of Fru^M Isoforms in Drosophila Olfactory Receptor Neurons.

Publications

Distinct Roles and Synergistic Function of Fru<sup>M</sup> Isoforms in Drosophila Olfactory Receptor Neurons.

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