Neuroscience
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The aim of the present work was to evaluate the potential activity of α-lactoalbumin (ALAC), a whey protein rich in tryptophan (TRP), in two rodent models of epileptogenesis and we explored a possible mechanism of action. The effects of ALAC (oral administration) were tested in two standard epileptogenesis protocols, namely the pilocarpine post-status epilepticus model in mice and the WAG/Rij rat model of absence epileptogenesis. The mechanism of action was investigated by assessing the effects of ALAC in two seizure models (N-methyl-d-aspartate (NMDA) and pentylenetetrazol (PTZ) -induced seizures) including d-serine co-administration. ⋯ ALAC is active in experimental models of seizure and epileptogenesis. Its effects are likely mediated by the inhibition of NMDA receptors at the glycine binding site, possibly secondarily to the in vivo enzymatic conversion of ALAC-generated tryptophan to kynurenic acid. However, other mechanisms of action contributing to ALAC effects cannot be excluded.
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Enteric viscerofugal neurons are interneurons with cell bodies in the gut wall; they project to prevertebral ganglia where they provide excitatory synaptic drive to sympathetic neurons which control intestinal motility and secretion. Here, we studied the mechanosensitivity and firing of single, identified viscerofugal neurons in guinea-pig distal colon. Flat sheet preparations of gut were set up in vitro and conventional extracellular recordings made from colonic nerve trunks. ⋯ They provide a significant primary afferent output from the colon, encoding circumferential length, largely independent of muscle tension. All viscerofugal neurons are directly mechanosensitive, although they have been reported to receive synaptic inputs. In short, viscerofugal neurons combine interneuronal function with length-sensitive mechanosensitivity.
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We investigated whether the "first trial effect" (FTE) in responses to support surface tilt has directional characteristics, or is simply due to a startle-like response. The FTE is the difference between the first (unpractised) trial response (FTR) and subsequent responses. ⋯ FTRs appear to consist of either a forward, backward or lateral movement strategy each imposed on an adapted response strategy. Only the lateral response shows a strong directional sensitivity. We hypothesise that FTR amplitudes result from a failure of the CNS to weight properly the stimulus metrics present in lower leg proprioceptive and vestibular inputs.
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Recently it has become apparent that microglia play a role not only in responding to insults within the central nervous system but also in responding to changes in synaptic activity and potentially modulating synaptic function. This has led to an enormous expansion of interest in how microglia respond to both pathological and nonpathological challenges, with activities that are associated with unique morphological transformations. Examining changes in microglial morphology can provide direct insight into the cells' functional activities, as morphological status is recognized to be tightly coupled with function. ⋯ This review critically examines the strengths and weaknesses of existing morphometric analysis procedures. This review further examines efforts to improve the utility of existing approaches and discusses new developments, such as digital reconstruction, that yield more accurate and specific information on how microglia remodel themselves. Ultimately, an improved understanding of the strengths and limitations of existing, and emerging, morphometric approaches will greatly facilitate efforts to understand how microglia remodel themselves in response to the full spectrum of challenges that they are known to encounter.
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The input synapses of cerebellar Purkinje cells (PCs) have been extensively studied and much has been learned about their dynamics, plasticity and functionality. In contrast there is limited information available about PC output synapses. This study uses dual cell recording methods to investigate synaptic dynamics and plasticity at individual PC synapses onto neighboring PCs in in vitro preparations of the mormyrid cerebellum. ⋯ For weak connections, however, the pre- and postsynaptic potentials are no longer synchronized, and presynaptic burst firing at intraburst rates of ∼50 Hz or higher is required to reliably induce the postsynaptic inhibition. A depression of this postsynaptic inhibition was observed for both types of connectivity following repeated presynaptic bursts, which was subsequently largely reversed following pairings of the presynaptic burst-induced IPSPs/IPSCs with evoked burst firing of the postsynaptic cell. Moreover, the original postsynaptic depression was found to be either augmented or reversed depending on the temporal order of each pair of additional pre- and postsynaptic cell activations, hence demonstrating a reversible and spike timing-dependent plasticity (STDP) at this synapse.