Brain Bag
Annie Homan "Presynaptic Homeostatic Plasticity at the Vertebrate Neuromuscular Synapse"
Homeostatic synaptic plasticity is an essential process by which a synapse is able to regulate its excitability to compensate for perturbations to the system. Presynaptic homeostatic plasticity centers on the mechanisms by which the nerve terminal alters neurotransmitter release in response to either reduced or enhanced postsynaptic activity. While presynaptic homeostatic plasticity has been well characterized in drosophila, this form of plasticity has not been well studied at vertebrate synapses. Here, we explore homeostatic regulation of neurotransmitter release at the vertebrate neuromuscular junction synapse. Following acute partial block of postsynaptic nicotinic acetylcholine receptors, we observed a compensatory increase in quantal content, a measure of the magnitude of neurotransmitter release. We did not observe an increase in quantal amplitude, suggesting a presynaptic locus for modulation. Additionally, we observed a dramatic increase in short-term depression during a 50 Hz stimulus train, further supporting the conclusion that short-term partial postsynaptic receptor blockade increases the probability of neurotransmitter release. Further, an enhancement of postsynaptic activity led to a compensatory decrease in quantal content. These data provide evidence that presynaptic modulation of neurotransmitter release can occur on a brief time scale in a vertebrate neuromuscular junction. The mechanisms for such plasticity, and the retrograde signal that induces presynaptic change following a postsynaptic receptor blockade are currently being studied. Presynaptic homeostatic plasticity is likely to be an important adaptation that contributes to physiological alterations in synaptic activity, disease adaptations, and treatment effects.
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Sweyta Lohani "Global fMRI effects of activation of Ventral Tegmental Area (VTA) dopamine neurons"
Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in cognitive and affective processing as well as in psychiatric illnesses including schizophrenia, ADHD and substance abuse disorders. In human studies, dopamine-related functions are routinely assessed using functional magnetic resonance imaging (fMRI) measures of blood oxygenation-level dependent (BOLD) signals during the performance of dopamine-dependent tasks. There is, however, a critical void in our knowledge about if and how activation of VTA dopamine neurons specifically influences regional or global fMRI signals. My research uses optogenetics in Th::Cre rats to selectively stimulate VTA dopamine neurons while simultaneously measuring global hemodynamic changes using BOLD and cerebral blood volume-weighted (CBVw) fMRI. We have found that phasic activation of VTA dopamine neurons increases BOLD and CBVw fMRI signals in VTA-innervated limbic regions, including the ventral striatum (nucleus accumbens). Surprisingly, the most prominent fMRI signal increase in the forebrain is observed in the dorsal striatum that is not traditionally associated with VTA dopamine neurotransmission. These data establish causation between phasic activation of VTA dopamine neurons and global fMRI signals. They further demonstrate that mesolimbic and non-limbic basal ganglia dopamine circuits are functionally connected and, thus, provide a novel framework for understanding dopamine-dependent functions and interpreting data obtained from human fMRI studies.