GABAergic (GABA ‫؍‬ ␥-aminobutyric acid) neurons from different brain regions contain high levels of parvalbumin, both in their soma and in their neurites. Parvalbumin is a slow Ca 2؉ buffer that may affect the amplitude and time course of intracellular Ca 2؉ transients in terminals after an action potential, and hence may regulate short-term synaptic plasticity. To test this possibility, we have applied paired-pulse stimulations (with 30-to 300-ms intervals) at GABAergic synapses between interneurons and Purkinje cells, both in wild-type (PV؉͞؉) mice and in parvalbumin knockout (PV؊͞؊) mice. We observed pairedpulse depression in PV؉͞؉ mice, but paired-pulse facilitation in PV؊͞؊ mice. In paired recordings of connected interneuronPurkinje cells, dialysis of the presynaptic interneuron with the slow Ca 2؉ buffer EGTA (1 mM) rescues paired-pulse depression in PV؊͞؊ mice. These data show that parvalbumin potently modulates short-term synaptic plasticity.GABA ͉ cerebellum ͉ basket cells ͉ stellate cells ͉ Purkinje cells T he immediate consequences of past neuronal activity on synaptic strength are often examined by measuring the ratio (called paired-pulse ratio, or PPR) between the mean synaptic current in response to a test stimulation over that obtained with a conditioning stimulus. If the PPR is larger than 1, the synapse is considered as facilitating, whereas values smaller than 1 are characteristic of depressing synapses. However, facilitation and depression presumably coexist in all experimental conditions, and the PPR that is measured may be viewed as a balance between these two competing processes (1, 2).Current hypotheses link facilitation to the fact that some of the Ca 2ϩ ions entering the presynaptic terminal during the first stimulus are still present when the second stimulus is delivered (3, 4). Several modes of action have been envisaged for the residual calcium. It could act by binding to high affinity sites of the normal exocytosis machinery (5), by binding to special sites responsible for facilitation (2, 6), or by modulating the degree of saturation of high affinity Ca 2ϩ buffers (7, 8), but direct evidence in favor of any of these possibilities is still lacking.Depression is a complex phenomenon including both pre-and postsynaptic components. It may involve depletion of a readily releasable pool of vesicles, saturation or desensitization of postsynaptic receptors, or still other processes (7, 9).Calcium-binding proteins such as parvalbumin (PV), calretinin, and calbindin D 28k are important modulators of intracellular calcium dynamics in neurons (10) and could therefore influence both facilitation and depression. Effects of these calcium buffers are determined by their affinities for Ca 2ϩ ions and by the kinetics (on and off rates) of binding and releasing of Ca 2ϩ . PV is in this regard interesting because it has a slow dissociation rate (about 1 s Ϫ1 ) and a slow apparent association rate (about 10 7 M Ϫ1 ⅐s Ϫ1 ), due to the fact that Mg 2ϩ ions compete with Ca 2ϩ ions for binding. As a result...

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Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.