The hypothalamic-neurohypophysial system undergoes dramatic morphological plasticity in response to physiological activation during parturition/lactation and dehydration, including somatic swelling, decreased glial coverage and increased synaptic innervation of the magnocellular neuroendocrine cells. Recent in-vitro electrophysiological studies in hypothalamic slices have demonstrated that coordinate changes in the synaptic physiology of the magnocellular neurons also occur under these conditions. Thus, the synaptic release of glutamate and GABA onto magnocellular neurons is increased during lactation and with chronic dehydration, and changes in postsynaptic glutamate and GABAA receptor expression lead to alterations of the functional properties of the glutamate and GABAA receptor channels. The presynaptic noradrenergic facilitation of glutamate release and inhibition of GABA release is also markedly enhanced following chronic dehydration. Additionally, both parturition and chronic dehydration are accompanied by an increase in the tonic activation of presynaptic metabotropic glutamate receptors due to the higher ambient glutamate concentration caused by decreased glial coverage and the resultant reduction in glutamate reuptake. Together, these electrophysiological studies reveal profound functional plasticity in the synaptic physiology of magnocellular neurons at parturition and following dehydration. The plastic changes support an increase in the excitability of magnocellular neuroendocrine cells by increasing glutamate inputs, decreasing GABA inputs, enhancing excitatory noradrenergic modulation, and reducing synaptic glutamatergic noise.