Whether an individual synapse releases single or multiple vesicles of transmitter per action potential is contentious and probably depends on the type synapse. One possibility that multivesicular release (MVR) determined by instantaneous probability ( P r ) therefore can be controlled activity-dependent changes in . We investigated across a range at synapses between Schaffer collaterals (SCs) CA1 pyramidal cells acute hippocampal slices using patch-clamp recordings. The size synaptic...

The goals of this study were to determine whether the long-term training regimens experienced by competitive collegiate swimmers would result in altered levels total and free serum insulin-like growth factor I (IGF-I) as well IGF-binding proteins (BP) IGFBP-1 -3. Two male (Teams 1M 2M) one female (Team 2F) teams studied at start training, after 2 mo 4 (2–4 had highest volume training), 5 (near end tapering; only for Team 1M), several days was over. For 1M, IGF-I concentrations increased 76%...

The discrete arrangement of voltage-gated K + (K v ) channels in axons may impart functional advantages action potential (AP) signaling yet, compact cell types, the organization is poorly understood. We find that cerebellar stellate interneurons mice, composition and influence populating axon diverse depends on location allowing axonal compartments to differentially control APs a local manner. 1 determine AP repolarization at spike initiation site but not more distal sites, limiting...

The cerebellum is hypothesized to represent timing information important for organizing salient motor events during periodically performed discontinuous movements. To provide functional evidence validating this idea, we measured and manipulated Purkinje cell (PC) activity in the lateral of mice trained volitionally perform periodic bouts licking regularly allocated water rewards. Overall, PC simple spiking modulated task performance, mapping phasic tongue protrusions retractions, as well...

Abstract Social recognition memory (SRM) is a key determinant of social interactions. While the cerebellum emerges as an important region for behavior, how cerebellar activity affects functions remains unclear. We selectively increased excitability molecular layer interneurons (MLIs) to suppress Purkinje cell firing in mouse vermis. Chemogenetic perturbation MLIs impaired SRM without affecting sociability, anxiety levels, motor coordination or object recognition. Optogenetic interference...

Abstract: NMDA receptors play a critical role in various aspects of CNS function. Hence, it is important to identify mechanisms that regulate receptor activity. We have shown previously insulin rapidly potentiates activity both native and recombinant expression systems. Here we report causes transient phosphorylation NR2A NR2B subunits on tyrosine residues. Rat hippocampal slices were exposed 1 μ M for 20 60 min then solubilized. immunoprecipitated probed phosphorylation. Insulin incubation...

Lateral inhibition is a common feature of cortical networks, serving such functions as contrast enhancement. In the olfactory bulb, imbedded in local connectivity at dendrodendritic synapses between mitral cells and interneurons. However, there also evidence for excitatory interactions despite lack direct synaptic connections. This lateral excitation, although less well recognized circuit, provides potentially powerful mechanism to enhance coordinated activity. We examined excitation paired...

In many neurons, subthreshold depolarization in the soma can transiently increase action-potential (AP)-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, part, due to relative inaccessibility axon direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily...

Inhibition from molecular layer interneurons (MLIs) is thought to play an important role in cerebellar function by sharpening the precision of Purkinje cell spike output. Yet coding features MLIs during behavior are poorly understood. To study MLI activity, we used vivo Ca2+ imaging head-fixed mice performance a rhythmic motor behavior, licking water consumption. were robustly active lick-related movement across lobule-specific region cerebellum showing high temporal correspondence within...

Mitral and tufted cells constitute the primary output of olfactory bulb. While are often considered as “displaced” mitral cells, their actual role in bulb processing has been little explored. We examined dendrodendritic inhibition between interneurons using whole cell voltage-clamp recording. Dendrodendritic inhibitory postsynaptic currents (IPSCs) generated by depolarizing voltage steps were completely blocked N-methyl-d-aspartate (NMDA) receptor antagonistd,l-2amino-5-phosphonopentanoic...

NMDA receptor (NMDAR)-dependent strengthening of neurotransmitter release has been widely observed, including in layer 5 (L5) pyramidal cells the visual cortex, and is attributed to axonal expression NMDARs. However, we failed detect NMDAR-mediated depolarizations or Ca 2+ entry L5 cell axons when focally stimulated with NMDAR agonists. This suggests that NMDARs are excluded from axon. In contrast, local GABA A activation alters excitability, indicating exclusion ligand-gated ion channels...

Motor learning involves neural circuit modifications in the cerebellar cortex, likely through re-weighting of parallel fiber inputs onto Purkinje cells (PCs). Climbing fibers instruct these synaptic when they excite PCs conjunction with activity, a pairing that enhances climbing fiber-evoked Ca2+ signaling PC dendrites. In vivo, spike continuously, including during movements are simultaneously conveying sensorimotor information to PCs. Whether activity motor behaviors is unknown. mice, we...

The cerebellar system helps modulate and fine-tune motor action. Purkinje cells (PCs) provide the sole output of cortex, therefore, any involvement in activity must be driven by changes PC firing rates. Several different cell types influence including excitatory input from parallel fibers inhibition molecular layer interneurons (MLIs). Similar to PCs, MLI is fibers, MLIs feed-forward onto PCs. To aid experimental assessment how contributes function behavior, we characterized a new knock-in...

Electron microscopy (EM) enables high-resolution visualization of protein distributions in biological tissues. For detection, gold nanoparticles are typically used as an electron-dense marker for immunohistochemically labeled proteins. Manual annotation particle labels is laborious and time consuming, counts can exceed 100,000 across hundreds image segments to obtain conclusive data sets. To automate this process, we developed Gold Digger, a software tool that uses modified pix2pix deep...

Dendrodendritic synapses, distributed along mitral cell lateral dendrites, provide powerful and extensive inhibition in the olfactory bulb. Activation of depends on effective penetration action potentials into dendrites. Although backpropagate with remarkable fidelity apical this issue is controversial for We used paired somatic dendritic recordings to measure proximal segments (0–200 μm from soma) potential-generated calcium transients monitor activity distal (200–600 soma). Somatically...

Abstract The signals in cerebellar Purkinje cells sufficient to instruct motor learning have not been systematically determined. Therefore, we applied optogenetics mice autonomously excite and measured the effect of this activity on plasticity induction adaptive behavior. Ex vivo, excitation channelrhodopsin-2-expressing elicits dendritic Ca 2+ transients with high-intensity stimuli initiating spiking that additionally contributes response. Channelrhodopsin-2-evoked potentiate co-active...

Duchenne muscular dystrophy (DMD), the most common form of childhood dystrophy, is caused by mutations in dystrophin gene. In addition to debilitating muscle degeneration, patients display a range cognitive deficits thought result from loss normally expressed brain. While function tissue well characterized, its role brain still poorly understood. The highest expression mouse cerebellar Purkinje cells (PCs), where it colocalizes with GABA A receptor clusters. Using ex vivo...

Abstract Climbing fibers supervise cerebellar learning by providing signals to Purkinje cells (PCs) that instruct adaptive changes mistakenly performed movements. Yet, climbing are regularly active, even during well movements, suggesting a mechanism dynamically regulates the ability of induce corrective plasticity in response motor errors. We found molecular layer interneurons (MLIs), whose inhibition PCs powerfully opposes climbing-fiber-mediated excitation, serve this function....