Basal synaptic strength can vary greatly between synapses formed by an individual neuron because of diverse probabilities of action potential (AP) evoked transmitter release ( ). Optical quantal analysis on large numbers of identified larval glutamatergic synapses shows that short-term plasticity (STP) also varies greatly between synapses made by an individual type I motor neuron (MN) onto a single body wall muscle. Synapses with high and low and different forms and level of STP have a random spatial distribution in the MN nerve terminal, and ones with very different properties can be located within 200 nm of one other. While synapses start off with widely diverse basal at low MN AP firing frequency and change differentially when MN firing frequency increases, the overall distribution of remains remarkably constant due to a balance between the numbers of synapses that facilitate and depress as well as their degree of change and basal synaptic weights. This constancy in transmitter release can ensure robustness across changing behavioral conditions.
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http://dx.doi.org/10.1101/2024.09.11.612562 | DOI Listing |
Biophys J
January 2025
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Bethesda, Maryland 20892, USA. Electronic address:
Dense-core vesicles (DCVs) are found in various types of cells, such as neurons, pancreatic β-cells, and chromaffin cells. These vesicles release transmitters, peptides, and hormones to regulate diverse functions, such as the stress response, immune response, behavior, and blood glucose levels. In traditional electron microscopy after chemical fixation, it is often reported that the dense cores occupy a portion of the vesicle towards the center and are surrounded by a clear halo.
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.
Synaptic vesicle (SV) trafficking toward the plasma membrane (PM) and subsequent SV maturation are essential for neurotransmitter release. These processes, including SV docking and priming, are co-ordinated by various proteins, such as SNAREs, Munc13 and synaptotagmin (Syt), which connect (tether) the SV to the PM. Here, we investigated how tethers of varying lengths mediate SV docking using a simplified mathematical model.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720.
Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, larvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G-coupled octopamine receptor (OAMB).
View Article and Find Full Text PDFCell Rep
January 2025
School of Neuroscience, Virginia Tech, Blacksburg, VA 24060, USA. Electronic address:
Words represent a uniquely human information channel-humans use words to express thoughts and feelings and to assign emotional valence to experience. Work from model organisms suggests that valence assignments are carried out in part by the neuromodulators dopamine, serotonin, and norepinephrine. Here, we ask whether valence signaling by these neuromodulators extends to word semantics in humans by measuring sub-second neuromodulator dynamics in the thalamus (N = 13) and anterior cingulate cortex (N = 6) of individuals evaluating positive, negative, and neutrally valenced words.
View Article and Find Full Text PDFbioRxiv
December 2024
Allen Institute, Seattle, WA 98109, USA.
In Parkinson's disease, dopaminergic neurons (DANs) in the midbrain gradually degenerate, with ventral substantia nigra pars compacta (SNc) DANs exhibiting greater vulnerability. However, it remains unclear whether specific molecular subtypes of ventral SNc DANs are more susceptible to degeneration in PD, and if they contribute to the early motor symptoms associated with the disease. We identified a subtype of + DANs, +, which are selectively lost earlier than other DANs, and with a time course that aligns with the development of motor symptoms in MitoPark mice.
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