Neuroscience
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To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings - combined with biocytin labelling - were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II-V of rat (postnatal days 17-22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appeared to coincide with the interneuron subclass; upon depolarisation, EPSPs received by multipolar non-adapting interneurons either decreased in amplitude or appeared insensitive, multipolar adapting interneuron EPSP amplitudes increased or appeared insensitive, whereas bitufted interneuron EPSP amplitudes increased or decreased. Connections were challenged with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP5) (50μM) revealing NMDA receptors to contribute to EPSPs received by all cell types, this also abolished the non-conventional voltage dependency. ⋯ The involvement of presynaptic NMDA receptors was indicated by coefficient of variation analysis and an increase in the failures of transmission. Furthermore, by loading MK-801 into the pre- or postsynaptic neurons, we observed that a reduction in inhibition requires presynaptic and not postsynaptic NMDA receptors. These results suggest that NMDA receptors possess pre- and postsynaptic roles at selective neocortical synapses that are probably important in governing spike-timing and information flow.
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Hyperpolarization-activated currents (I(h)) affect multiple neuronal functions including membrane potential, intrinsic firing properties, synaptic integration and frequency-dependent resonance behavior. Consistently, I(h) plays a key role for oscillations at the cellular and network level, including theta and gamma oscillations in rodent hippocampal circuits. Little is known, however, about the contribution of I(h) to a prominent memory-related pattern of network activity called sharp-wave-ripple complexes (SPW-R). ⋯ Likewise, coupling between field oscillations and units was unchanged, showing unaltered recruitment of neurons into oscillating assemblies. Control experiments exclude a contribution of T-type calcium channels to the observed effects. Together, we report a specific contribution of hyperpolarization-activated cation currents to the generation of sharp waves in the hippocampus.
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The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. ⋯ Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.
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Approximately 50% of patients with a major depressive episode fail to achieve remission with first-line antidepressant treatments. Second-line treatment strategies for such patients include lithium augmentation of antidepressants, particularly with tricyclic antidepressants. The neurobiological mechanisms underlying the therapeutic effects of lithium augmentation are not yet fully understood. ⋯ Since chronic treatment with antidepressant drugs increases the proliferation of newly-born cells in the hippocampus, and hippocampal cell proliferation is required for the behavioural effects of at least some antidepressants in neohypophagia tests, the present study also investigated whether lithium plus desipramine increased cell proliferation in the hippocampus. Chronic treatment with lithium plus desipramine but neither drug alone, induced antidepressant-like behaviour and increased hippocampal cell proliferation, thus suggesting that increased hippocampal cell proliferation may be a mechanism underlying lithium augmentation of antidepressants. Moreover, since BALB/cOLaHsd mice respond to lithium plus desipramine but not to either drug alone, they may become useful in the development of a mouse model of treatment-refractory depression for which there is an unmet need.
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The intergeniculate leaflet (IGL) of the lateral geniculate body in the rat is a population of GABAergic neurons that can be divided into two, anatomically and neurochemically distinct populations. One population comprises neuropeptide-Y (NPY)-positive neurons that form the geniculohypothalamic tract innervating the suprachiasmatic nuclei (SCN) and the other population comprises enkephalin-positive (ENK) neurons giving rise to the geniculo-geniculate tract innervating the contralateral IGL (cIGL). Previous electrophysiological studies have observed various patterns of firing and different responses to changes in lighting conditions of IGL neurons in vitro and in vivo. ⋯ In contrast, all IGL neurons identified as projecting to the SCN displayed a low level of firing in the light and a majority of these cells increased firing in the darkness. All IGL neurons projecting to the SCN were characterised by an irregular pattern of firing in the light and dark. These data are the first to demonstrate that differentially projecting rat intergeniculate leaflet neurons are characterised by distinct firing patterns and opposite responses to light and dark conditions.