Time course and magnitude of ventilatory and renal acid-base acclimatization following rapid ascent to and residence at 3,800 m over nine days.

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a).

Altered chloride homeostasis removes synaptic inhibitory constraint of the stress axis.

In mammals, stress elicits a stereotyped endocrine response that requires an increase in the activity of hypothalamic parvocellular neuroendocrine neurons. The output of these cells is normally constrained by powerful GABA-mediated synaptic inhibition. We found that acute restraint stress in rats released the system from inhibitory synaptic drive in vivo by down-regulating the transmembrane anion transporter KCC2.

Brain-derived neurotrophic factor silences GABA synapses onto hypothalamic neuroendocrine cells through a postsynaptic dynamin-mediated mechanism.

In the paraventricular nucleus of the hypothalamus (PVN), experimental stress paradigms that suppress gamma-aminobutyric acid (GABA) inputs to parvocellular neuroendocrine cells (PNCs) also increase the expression of brain-derived neurotrophic factor (BDNF). In the adult CNS, BDNF regulates the efficacy of GABAergic transmission, but its contributions to functional changes at inhibitory synapses in the PVN have not been investigated. Analysis of quantal transmission revealed a decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in response to BDNF with no accompanying changes in their amplitude.

Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy.

Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established.

Dopamine modulates use-dependent plasticity of inhibitory synapses.

The release of the hormones oxytocin (OT) and vasopressin (VP) into the circulation is dictated by the electrical activity of hypothalamic magnocellular neurosecretory cells (MNCs). In the paraventricular nucleus of the hypothalamus (PVN), MNC neuronal activity is exquisitely sensitive to changes in input from inhibitory GABAergic synapses. To explore the hypothesis that efficacy at these synapses is dictated by the rate at which a given synapse is activated, we obtained whole-cell recordings from MNCs in postnatal day 21-27 male Sprague Dawley rat brain slices.