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Journal of neuroendocrinology (1)
Progress in Brain Research (1)
The Journal of neuroscience : the official journal of the Society for Neuroscience (1)
Teruyama, Ryoichi (3)
Armstrong, William E. (1)
Brush, Benjamin R. (1)
Del Negro, Christopher A. (1)
Feldman, Jack L. (1)
Haam, Juhee (1)
Halmos, Katalin C. (1)
Hayes, John A. (1)
Li, Chunyan (1)
Morton, Linda A. (1)
Pace, Ryland W. (1)
Popescu, Ion R. (1)
Tasker, Jeffrey G. (1)
Ueta, Yoichi (1)
Wang, Lie (1)
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GABA Is Excitatory in Adult Vasopressinergic Neuroendocrine Cells
Popescu, Ion R.
Morton, Linda A.
Halmos, Katalin C.
Tasker, Jeffrey G.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Neuronal excitability in the adult brain is controlled by a balance between synaptic excitation and inhibition mediated by glutamate and GABA, respectively. While generally inhibitory in the adult brain, GABAA receptor activation is excitatory under certain conditions in which the GABA reversal potential is shifted positive due to intracellular Cl− accumulation, such as during early postnatal development and brain injury. However, the conditions under which GABA is excitatory are generally either transitory or pathological. Here, we reveal GABAergic synaptic inputs to be uniformly excitatory in vasopressin (VP)-secreting magnocellular neurons in the adult hypothalamus under normal conditions. The GABA reversal potential (EGABA) was positive to resting potential and spike threshold in VP neurons, but not in oxytocin (OT)-secreting neurons. The VP neurons lacked expression of the K+-Cl− co-transporter 2 (KCC2), the predominant Cl− exporter in the adult brain. The EGABA was unaffected by inhibition of KCC2 in VP neurons, but was shifted positive in OT neurons, which express KCC2. Alternatively, inhibition of the Na+-K+-Cl− co-transporter 1 (NKCC1), a Cl− importer expressed in most cell types mainly during postnatal development, caused a negative shift in EGABA in VP neurons, but had no effect on GABA currents in OT neurons. GABAA receptor blockade caused a decrease in the firing rate of VP neurons, but an increase in firing in OT neurons. Our findings demonstrate that GABA is excitatory in adult VP neurons, suggesting that the classical excitation/inhibition paradigm of synaptic glutamate and GABA control of neuronal excitability does not apply to VP neurons.
Synaptically Activated Burst-Generating Conductances Underlie a Group-Pacemaker Mechanism for Respiratory Rhythm Generation in Mammals
Del Negro, Christopher A.
Hayes, John A.
Pace, Ryland W.
Brush, Benjamin R.
Feldman, Jack L.
Progress in Brain Research
Breathing, chewing and walking are critical life-sustaining behaviors in mammals that consist essentially of simple rhythmic movements. Breathing movements in particular involve the diaphragm, thorax, and airways but emanate from a network in the lower brain stem. This network can be studied in reduced preparations in vitro and using simplified mathematical models that make testable predictions. An iterative approach that employs both in vitro and in silico models has ruled out canonical mechanisms for respiratory rhythm that involve reciprocal inhibition and pacemaker properties. We present an alternative model in which emergent network properties play the key rhythmogenic role. Specifically, we show evidence that synaptically activated burst-generating conductances – which are only available in the context of network activity – engender robust periodic bursts in respiratory neurons. Because the cellular burst-generating mechanism is linked to network synaptic drive we dub this type of system a group pacemaker.
preBötzinger Complex; pre-Bötzinger Complex; central pattern generator (CPG); metabotropic glutamate receptors; calcium-activated nonspecific cation current; mathematical models; emergent network properties; breathing
Performance, properties, and plasticity of identified oxytocin and vasopressin neurones in vitro
Armstrong, William E.
Journal of neuroendocrinology
The neurohypophysial hormones oxytocin (OT) and vasopressin (VP) originate from hypothalamic neurosecretory cells in the paraventricular and supraoptic (SON) nuclei. The firing rate and pattern of action potentials arising from these neurones determine the timing and quantity of peripheral hormone release. We have used immunochemical identification of biocytin-filled SON neurones in hypothalamic slices in vitro to uncover differences between OT and VP neurones in membrane and synaptic properties, firing patterns, and plasticity during pregnancy and lactation. In this review we summarise some recent findings from this approach: 1) VP neuronal excitability is influenced by slow (sDAP) and fast (fDAP) depolarising afterpotentials that underlie phasic bursting activity. The fDAP may relate to a transient receptor potential (TRP) channel, type melastatin (TRPM4 and/or TRPM5), both of which are immunochemically localised more to VP neurones, and especially, to their dendrites. Both TRPM4 and TRPM5 mRNAs are found in the SON, but single cell RT-PCR suggestsTRPM4 might be the more prominent channel. Phasic bursting in VP neurones is little influenced by spontaneous synaptic activity in slices, being shaped largely by intrinsic currents. 2) The firing pattern of OT neurones ranges from irregular to continuous, with the coefficient of variation determined by randomly distributed, spontaneous GABAergic, inhibitory synaptic currents (sIPSCs). These sIPSCs are 4–5 fold more frequent in OT vs. VP neurones, and much more frequent than spontaneous excitatory synaptic currents. 3) Both cell types express Ca++-dependent afterhyperpolarisations (AHPs), including an apamin-sensitive, medium duration AHP and a slower, apamin-insensitive AHP (sAHP). In OT neurones, both AHPs are enhanced during pregnancy and lactation. During pregnancy, the plasticity of the sAHP is blocked by antagonism of central OT receptors. AHP enhancement is mimicked by exposing slices from Day 19 pregnant rats to OT and oestradiol, suggesting central OT and sex steroids program this plasticity during pregnancy by direct hypothalamic actions. In conclusion, the differences in VP and OT neuronal function are underlain by differences in both membrane and synaptic properties, and differentially modulated by reproductive state.
afterhyperpolarisation; depolarising afterpotential; electrophysiology; pregnancy; lactation
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