Restoration of Frequency-Dependent Depression of the H-Reflex by Passive Exercise in Spinal Rats

Hyper-reflexia, measured as a decrease of low frequency-dependent depression of the H-reflex, is known to occur in both humans and animals after spinal cord injury (SCI). Previous studies have shown that passive exercise for 3 months could be used to restore low frequency-dependent depression of the H-reflex after SCI. To determine the effects of various periods of time on the ability of passive exercise to restore low frequency-dependent depression of the H-reflex. Spinal Cord Injury Mobilization Program of the Center for Translational Neuroscience, the research arm of the Jackson T Stephens Spine and Neuroscience Institute, Little Rock, AR, USA. Adult rats underwent complete spinal cord transection at the T10 level. The hindlimbs were passively exercised in different groups of rats for 1 h/day, 5 days/week for 15, 30, 45, 60, or 90 days, and low frequency-dependent depression of the H-reflex was tested. Statistically significant low frequency-dependent depression of the H-reflex was evident by 30 days of exercise, although numerical reductions were seen even at 15 days. There was a linear decrease in low frequency-dependent depression of the H-reflex with duration of passive exercise. Passive exercise can restore frequency-dependent depression of spinal reflexes in a time-dependent manner if used following complete spinal transection

Long-term potentiation in frontal cortex: Role of NMDA-modulated polysynaptic excitatory pathways

The present study examined the role of N-methyl-D-aspartic acid (NMDA) receptors in synaptic plasticity in regular-spiking cells of rat frontal cortex. Intracortical stimulation, at levels subthreshold for elicitation of action potentials, evoked a late excitatory postsynaptic potential (EPSP) in layer II III neurons that was sensitive to the selective NMDA antagonist -2-amino-5-phosphonovaleric acid (APV). This late EPSP showed marked short-term frequency-dependent depression, suggesting that it is polysynaptic in origin. Polysynaptic late EPSPs were selectively enhanced following high-frequency stimulation. This sustained increase in synaptic efficacy, or long-term potentiation, was expressed in regular spiking cells and appeared to result from activation of NMDA receptors on excitatory interneurons. These data demonstrate the existence of an NMDA-modulated polysynaptic circuit in the neocortex which displays several types of use-dependent plasticity

Calmodulin mediates rapid recruitment of fast-releasing synaptic vesicles at a calyx-type synapse.

In many synapses, depletion and recruitment of releasable synaptic vesicles contribute to use-dependent synaptic depression and recovery. Recently it has been shown that high- frequency presynaptic stimulation enhances recovery from depression, which may be mediated by Ca2+. We addressed this issue by measuring quantal release rates at the calyx of Held synapse and found that transmission is mediated by a heterogeneous population of vesicles, with one subset releasing rapidly and recovering slowly and another one releasing reluctantly and recovering rapidly. Ca2+ promotes refilling of the rapidly releasing synaptic vesicle pool and calmodulin inhibitors block this effect. We propose that calmodulin- dependent refilling supports recovery from synaptic depression during high-frequency trains in concert with rapid recovery of the slowly releasing vesicles

Demographic profile and associations of dialysis dependent chronic kidney disease patients in federal capital of pakistan.

Depression is quite prevalent in patients with chronic kidney disease. Knowing the frequency of depression in such patients and its association with different variables may be helpful in devising strategies for better and timely management of such patients in our setup. Materials and methods: This cross sectional study was conducted by recruiting 315 patients of either gender, ≥ 18 years of age with chronic kidney disease (CKD) and receiving care at Pakistan Institute of Medical Sciences, Islamabad. Patients were divided into two groups; group A: pre-dialysis and group B: dialysis (End Stage Renal Disease). Prevalence of depression in CKD and dialysis group and its association with gender, level of formal education and socioeconomic status was evaluated using descriptive statistics and chi-square test. Results: Out of 204 (100%) patients in group B, 171 (83.8%) patients had depression while in group A, 68 (61.3%) out of 111 (100%) patients were depressed. The prevalence of depression in all stages of CKD combined was 75.87 % (239 out of 315) and that in dialysis group was 83.82% (171 out of 204). Frequency of depression was significantly higher in the dialysis group (p=0.01). Those with higher level of education less commonly suffered from depression (p=0.01). No such association was found with gender (p=0.68) or socioeconomic status (p=0.12).Conclusion: Frequency of depression is significantly higher in dialysis dependent CKD patients with an overall prevalence of 75.87% in CKD and 83.82% in dialysis dependent ones. Higher level of formal education positively affects the outcome while gender and socioeconomic class have no significant association

Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses

Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGluf) and ultrafast (iGluu) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGluu has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGluu is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGluu responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons

Frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pools that are differentially poised for exocytosis shapes short-term plasticity. However, the frequency-dependent mobilization of these sub-pools is poorly understood. Using slice recordings and modeling of synaptic activity at cerebellar granule cell to Purkinje cell synapses of mice, we describe two sub-pools in the RRP that can be differentially recruited upon ultrafast changes in the stimulation frequency. We show that at low frequency stimulations, a first sub-pool is gradually silenced, leading to full blockage of synaptic transmission. Conversely, a second pool of synaptic vesicles that cannot be released by a single stimulus is recruited within milliseconds by high-frequency stimulation and support an ultrafast recovery of neurotransmitter release after low-frequency depression. This frequency-dependent mobilization or silencing of sub-pools in the RRP in terminals of granule cells may play a role in the filtering of sensorimotor information in the cerebellum