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Schlueter, O.

Publications and source records attributed to Schlueter, O..

3 recordsLinked to original sources

Temporal Dynamics of Nucleus Accumbens Neurons in Male Mice During Reward Seeking

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca2+ activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca2+ activity: approximately 0, -2.5 or -5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at -5 sec or D2-neurons at -2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior.

neuroscience↗

An unconventional GABAergic circuit differently controls pyramidal neuron activity in two visual cortical areas via endocannabinoids

Perisomatic inhibition of neocortical pyramidal neurons (PNs) coordinates cortical network activity during sensory processing, and it has been mainly attributed to parvalbumin-expressing basket cells (BCs). However, cannabinoid receptor type 1 (CB1)-expressing interneurons also inhibit the perisomatic region of PNs but the connectivity and function of these elusive - yet prominent - neocortical GABAergic cells is unknown. We found that the connectivity pattern of CB1-positive BCs strongly differs between primary and high-order cortical visual areas. Moreover, persistently active CB1 signaling suppresses GABA release from CB1 BCs in the medial secondary visual cortex (V2M), but not in the primary (V1) visual area. Accordingly, in vivo, tonic CB1 signaling is responsible for higher but less coordinated PN activity in V2M than in V1. Our results indicate a differential CB1-mediated mechanism controlling PN activity, and suggest an alternative connectivity schemes of a specific GABAergic circuit in different cortical areas

neuroscience↗

Enhancement of synaptic AMPA receptors depends mutually on Src and PSD-95

Synaptic incorporation and removal of AMPA receptors is highly regulated to modulate the strength of synaptic transmission for long-term synaptic plasticity during brain development and associative learning. PSD-932 and PSD-95, two paralogs of the DLG-MAGUK protein family of signaling scaffolds govern the synaptic incorporation and stabilization of AMPA receptors opposingly, with PSD-95 promoting and PSD-932 inhibiting it. The associated signaling mechanisms that control the synaptic incorporation and stabilization remain elusive. Here, we used domain swapping between the antagonizing signaling scaffolds to identify the protein motifs responsible for enhancing synaptic AMPA receptors and the associated signaling protein. We narrowed down multiple motifs in the N-terminal domain that are principally responsible for governing the enhancement by Src. Specific activation and inhibiting peptides revealed continuous activity of Src. Together, the results depict a mutual dependence of Src and PSD-95 in enhancing and maintaining synaptic AMPA receptors.

neuroscience↗