Biology subjects

Rayport, S.

Publications and source records attributed to Rayport, S..

6 recordsLinked to original sources

bioRxiv2023

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

Parkinsons disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1{beta} as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.

neuroscience↗

bioRxiv2021

Single dose of amphetamine induces delayed subregional attenuation of striatal cholinergic interneuron activity

Psychostimulants such as amphetamine target dopamine neuron synapses to engender drug-induced plasticity. While dopamine neurons modulate the activity of striatal cholinergic interneurons (ChIs) with regional heterogeneity, how amphetamine affects ChI activity has not been elucidated. Here, we applied quantitative fluorescence imaging approaches to map the dose-dependent effects of a single dose of amphetamine on ChI activity at 2.5 and 24 hours after injection across the mouse striatum using the activity-dependent marker phosphorylated ribosomal protein S6 (p-rpS6). We found that amphetamine did not induce neurotoxic effects on ChIs, as their distribution and morphology were not affected. While low- or high-dose amphetamine did not affect ChI activity after 2.5 hours, ChI activity was significantly reduced in all striatal subregions after 24 hours, with a dose-dependent effect in the nucleus accumbens. Thus, our findings suggest that a single dose of amphetamine has delayed regionally heterogeneous effects on ChI activity. Significance statementUsing the activity dependent marker phosphorylated ribosomal protein S6 (p-rpS6), we mapped amphetamine effects on the activity of cholinergic interneurons (ChIs) across the striatum. Amphetamine caused a delayed attenuation of ChI activity in all striatal subregions, and a dose-dependent effect in the ventral striatum/nucleus accumbens, a critical site of psychostimulant action.

neuroscience↗

bioRxiv2020

Dopamine neuron synaptic connectivity defines physiological striatal domains

Dopamine neurons projecting to the striatum control movement, cognition, and motivation. They do so via slower, dopamine volume transmission and also via faster synaptic dopamine, glutamate and GABA transmission. To define the scope of these synaptic actions, we recorded dopamine neuron synaptic currents in the four major classes of striatal neurons. This revealed that dopaminergic and GABAergic synaptic actions are widespread; glutamatergic synaptic actions are robust in the medial nucleus accumbens and the anterolateral dorsal striatum, mediating fast and slow excitation, respectively. Dopamine neuron synaptic actions in cholinergic interneurons are the strongest and most complex, involving all three transmitters, their multiple receptors, and are the most regionally heterogeneous. The caudal striatum forms a single domain with overall weak dopamine neuron synaptic actions. This synaptic mapping reveals that dopamine neuron synaptic actions extend across the entire striatum, are regionally heterogeneous and organized in physiological domains, determined mainly by their excitatory actions.

neuroscience↗

bioRxiv2018

Substantia nigra dopamine neurons evoke a delayed excitation in lateral dorsal striatal cholinergic interneurons via glutamate cotransmission

Dopamine neurons have different synaptic actions in the ventral and dorsal striatum (dStr), but whether this heterogeneity extends to dStr subregions has not been addressed. We have found that optogenetic activation of dStr dopamine neuron terminals in mouse brain slices pauses the firing of cholinergic interneurons in both the medial and lateral subregions, while in the lateral subregion the pause is shorter due to a subsequent excitation. This excitation is mediated mainly by metabotropic glutamate receptor 1 (mGluR1) and partially by dopamine D1-like receptors coupled to transient receptor potential channel 3 and 7. DA neurons do not signal to spiny projection neurons in the medial dStr, while they elicit ionotropic glutamate responses in the lateral dStr. The DA neurons mediating these excitatory signals are in the substantia nigra (SN). Thus, SN dopamine neurons engage different receptors in different postsynaptic neurons in different dStr subregions to convey strikingly different signals.

neuroscience↗

bioRxiv2017

Skin photoreceptors in the leopard frog

INTRODUCTION INTRODUCTION EXPERIMENTAL METHODS OBSERVATIONS DISCUSSION ELECTODERMOGRAM MECHANISM CONCLUDING REMARKS REFERENCES It is an engaging thought that the great sense organs concentrated in the head region of vertebrates were all derived from primitive systems of widely diffused skin receptors. In this sense, one can think of the receptors of hearing as derived from cutaneous touch spots, with which they share many physiological properties; the organ of equilibrium the cristae of the semicircular canals from deep pressure receptors; smell from chemoreceptors that remain widely distributed over the bodies of the mucous - skinned fishes and amphibia and have withdrawn into the mucous area of the mouth in land vertebrates. In all these cases, the transition from skin receptors to sense org ...

neuroscience↗

bioRxiv2017

Dopamine neuron dependent behaviors mediated by glutamate cotransmission

Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate the behavioral role of the cotransmission, we targeted the glutamate-recycling enzyme glutaminase (gene GLS1). In mice with a DAT-driven conditional heterozygous (cHET) reduction of GLS1 in their dopamine neurons, dopamine neuron survival and transmission were unaffected, while glutamate cotransmission at phasic firing frequencies was reduced, enabling focusing the cotransmission. DAT GLS1 cHET mice showed normal emotional and motor behaviors, and an unaffected response to acute amphetamine. Strikingly, amphetamine sensitization was reduced and latent inhibition potentiated. These behavioral effects, also seen in global GLS1 HETs with a schizophrenia resilience phenotype, were not seen in mice with an Emx1-driven forebrain reduction affecting most brain glutamatergic neurons. Thus, a reduction in dopamine neuron glutamate cotransmission appears to mediate significant components of the GLS1 HET schizophrenia resilience phenotype, and glutamate cotransmission appears to be important in attribution of motivational salience.

neuroscience↗