Neuroscience
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The subthalamic nucleus (STN) modulates the activity of globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) neurons via its direct glutamatergic projections. To investigate the mechanism by which STN affects activity in these structures and whether STN induced activity is comparable among STN target neurons, we performed patch clamp recordings in a tilted, parasagittal, basal ganglia slice (BGS) that preserves these functional connections. We report that single, brief stimulation of the STN generates a brief monosynaptic AMPA-mediated excitatory postsynaptic current (EPSC) in GP, EP and SNr neurons. ⋯ They were eliminated by surgical removal of the STN from the BGS slice, indicating that the STN is required for their generation. Reconstruction of biocytin-filled STN neurons revealed that a third of STN neurons project intra-STN axon collaterals that may underlie polysynaptic activity. We propose that activation of the STN yields comparable long lasting excitations in its target neurons by means of a polysynaptic network.
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Brain derived nerve factor (BDNF) is a trophic factor belonging to the neurotrophin family. It is upregulated in various inflammatory conditions, where it may contribute to altered pain states. In cystitis, little is known about the relevance of BDNF in bladder-generated noxious input and bladder overactivity, a matter we investigated in the present study. ⋯ TrkB-Ig(2) also reduced spinal extracellular signal-regulated kinase (ERK) activation, it is possible that BDNF contribution to inflammation-induced bladder hyperactivity is via spinal activation of the ERK pathway. Finally, the reduction in c-Fos expression indicates that TrkB-Ig(2) also reduced bladder-generated noxious input. Our results show that sequestration of BDNF may be considered a new therapeutic strategy to treat chronic cystitis.
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Osmotherapy with 10% hypertonic saline (HS) alleviates cerebral edema through osmotic force. Aquaporin-4 (AQP4) has been reported to be implicated in the pathogenesis of cerebral edema resulting from a variety of brain injury. This study aimed to determine if 10% hypertonic saline ameliorates cerebral edema through downregulation of AQP4 expression in the perivascular astrocytes in the ischemic cerebral edema. ⋯ Concomitantly, downregulated expression of AQP4 in the perivascular astrocytes after 10% HS treatment was observed. Our results suggest that in addition to its osmotic force, 10% HS exerts anti-edema effects possibly through downregulation of AQP4 expression in the perivascular astrocytes. The reduction of brain edema after 10% HS administration can prevent ischemic brain damage.
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The medial septum diagonal band complex (MS/DB) projects via cholinergic and GABAergic pathways to the hippocampus and plays a key role in the hippocampal theta rhythm. In the MS/DB we have previously described a population of fast spiking GABAergic neurons that contain parvalbumin and mediate theta frequency activity in vitro. The Kv3.1 potassium channel is a delayed rectifier channel that plays a major role in fast spiking neurons in the CNS, and has previously been localized in the MS/DB. ⋯ Electrophysiological studies were also carried out on rat MS/DB slices to examine the role of the Kv3.1 channel in theta frequency oscillations. The results for the MS/DB were as follows: (1) cholinergic cells did not express GFP in either GAD67-GFP or VGluT2-GFP mice, and there was GAD67 immunoreactivity in GFP-positive neurons in GAD67-GFP mice and in a small proportion (6%) of GFP-positive neurons in VGluT2-GFP mice. (2) Kv3.1b immunofluorescence was associated with the somata of GABAergic neurons, especially those that contained parvalbumin, and with a minority of glutamatergic neurons, but not with cholinergic neurons, and with GABAergic axonal terminal-like processes around certain GABAergic neurons. (3) Both Kv3.1b-positive and -negative GABAergic neurons were septo-hippocampal, and there was a minor projection to hippocampus from VGluT2-GFP neurons. (4) Kainate-induced theta oscillations in the MS/DB slice were potentiated rather than inhibited by the Kv3.1 blocker 4-aminopyridine, and this agent on its own produced theta frequency oscillations in MS/DB slices that were reduced by ionotropic glutamate and GABA receptor antagonists and abolished by low extracellular calcium. These studies confirm the presence of heterogeneous populations of septo-hippocampal neurons in the MS/DB, and suggest that presence of Kv3.1 in the GABAergic neurons does not contribute to theta activity through fast spiking properties, but possibly by the regulation of transmitter release from axonal terminals.
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We previously reported that electrical stimulation of the reticular formation dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at short latencies and that RdVII neurons were antidromically activated by stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory premotor neurons targeting the MoV are likely located in the RdVII. We thus examined the properties of synaptic transmission from the RdVII to jaw-closing and jaw-opening motoneurons in horizontal brainstem preparations from developing rats using voltage-sensitive dye, patch-clamp recordings and laser photostimulation. Electrical stimulation of the RdVII evoked optical responses in the MoV. ⋯ In P8-11 rats, electrical stimulation of the RdVII also evoked PSCs in all 14 masseter motoneurons tested, and the effects of the antagonists on the PSCs were similar to those in P1-4 rats. On the other hand, RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested. These results suggest that both neonatal and juvenile jaw-closing motoneurons receive strong synaptic inputs from the RdVII through activation of glutamate, glycine and GABA(A) receptors, whereas inputs from the RdVII to jaw-opening motoneurons seem to be weak.