Sessa, A. | bioRxiv Science

bioRxiv2019

SULTA4A1 modulates synaptic development and function by promoting the formation of PSD-95/NMDAR complex

Sulfotransferase 4A1 (SULT4A1) is a cytosolic sulfotransferase, that is highly conserved across species and extensively expressed in the brain. However, the biological function of SULT4A1 is unclear. SULT4A1 has been implicated in several neuropsychiatric disorders, such as Phelan-McDermid Syndrome and schizophrenia. Here, we investigate the role of SULT4A1 within neuron development and function. Our data demonstrate that SULT4A1 modulates neuronal branching complexity and dendritic spines formation. Moreover, we show that SULT4A1, by negatively regulating the catalytic activity of Pin1 towards PSD-95, facilitates NMDAR synaptic expression and function. Finally, we demonstrate that the pharmacological inhibition of Pin1 reverses the pathological phenotypes of SULT4A1 knockdown neurons by specifically restoring dendritic spine density and rescuing NMDAR-mediated synaptic transmission. Together, these findings identify SULT4A1 as a novel player in neuron development and function by modulating dendritic morphology and synaptic activity.

neuroscience↗

bioRxiv2019

Somatostatin-Expressing Interneurons Co-Release GABA and Glutamate onto Different Postsynaptic Targets in the Striatum.

The functional contribution of somatostatin-expressing interneurons (SST-INs) to the synaptic organization of the striatum is poorly understood. Using electrophysiological recordings, optogenetic stimulation, and single-cell PCR analysis, we investigated functional patterns of synaptic connectivity in striatal SST-INs expressing channelrhodopsin-2. Photostimulation of these cells induced both glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) in striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs). The two synaptic components showed equally fast onset latencies, suggesting a mechanism of co-transmission. Accordingly, single-cell PCR analysis revealed that individual striatal SST-INs expressed mRNAs for both glutamate and GABA vesicular transporters (VGLUT1 and VGAT, respectively). During relatively prolonged optical stimuli (0.5-1s), IPSC arrays consistently outlasted EPSCs. As a result, photostimulation of SST-INs caused a transient burst of action potentials followed by a prolonged inhibition in postsynaptic cells.\n\nThese data suggest that striatal SST-INs are specialized to locally project synapses exerting a composite excitatory and inhibitory effect through GABA/glutamate co-transmission onto different postsynaptic targets.

neuroscience↗