Apical dendrites and somata of layer V pyramidal neurons were recorded with tight-seal patch electrodes in a slice preparation of rat somatosensory cortex. Recording sites were confirmed by measurements of the electrode location and by staining with biocytin. Dendritic recordings were made along the main trunk of the apical dendrite, usually within layer IV, at distances from 100 to 500 microns from the soma. Most cells recorded through the dendrite had a distinct enlargement of the apical trunk around the presumed recording site. The electrical properties of apical dendrites were readily distinguishable from those of somata. Dendrites generated two types of response when injected with depolarizing current. Group I responses were relatively small and broad Na(+)-dependent action potentials whose amplitude and rate-of-rise were negatively correlated with recording distance from the soma. Group II responses were complex, clustered firing patterns of Na(+)-dependent spikes together with higher-threshold slow spikes or plateaus; in these dendrites spike parameters were not correlated with distance from the soma. These two response groups were correlated with dendritic morphology: group I had significantly fewer oblique branches on the apical dendrite (5.5 vs 12.0) and a thinner apical trunk (2.0 vs 2.5 microns) than group II. TTX (1-2 microM) selectively blocked fast dendritic spikes, but not slow spikes and plateaus. Blocking Ca2+ currents reduced complex firing patterns and suppressed high-threshold slow spikes. Physiological and pharmacological studies imply that slow spikes and plateau potentials were primarily generated by high-threshold Ca2+ channels in the apical dendrite. Stimulating axons of layer I elicited EPSPs on distal apical dendrites of layer V cells. Recordings from both groups of apical dendrites revealed that EPSPs triggered a variety of distally generated, all-or-nothing depolarizations. The results show that voltage-dependent Na+ and Ca2+ currents are present in distal apical dendrites, in variable densities. These currents significantly modify distal synaptic events. The prevalence and character of active dendritic spiking (and presumably of Na+ and Ca2+ channel densities) correlate with the morphology of the apical dendritic tree.

Neurotrophins have traditionally been regarded as slowly acting signals essential for neuronal survival and differentiation. However, brain-derived neurotrophic factor and neurotrophin 3 (NT-3) have recently been reported to exert an acute potentiation ofsynaptic activity at the amphibian neuromuscular junction. Little is known about the role of neurotrophins on functional synapses in the central nervous system. Here we show that NT-3 rapidly increased the frequency of spontaneous action potentials, and it synchronized excitatory synaptic activities in developing cortical neurons. Moreover, the inhibitory synaptic transmission mediated by -aminobutyric acid (GABA) subtype A receptors was found to be reduced by NT-3. Thus, the excitatory effects of NT-3 on spontaneous action potentials were attributable to a reduction of GABAergic transmission. Our findings, together with previous reports of rapid regulation of central nervous system neurotrophin expression by neuronal activity and of the role of GABAergic transmission in cortical plasticity, suggest a mechanism for modulation of synaptic transmission and activitydependent synaptic modulation in cortical neurons.Extensive studies in the past few years have elucidated the important roles that the neurotrophins [including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5)] play in the development and maintenance of both peripheral and central nervous systems (for recent reviews see refs. 1 and 2). The functions of neurotrophins on distinct neuronal populations are mediated by the cellular expression of the trk family of tyrosine kinase receptors (3,4). While the effects of neurotrophins on neuronal survival and differentiation are well established, little is known about their role in synaptic development and function. Moreover, the classic view of neurotrophins stresses their long-lasting, chronic actions. However, a recent study showed that BDNF and NT-3 rapidly enhance synaptic activity at developing neuromuscular junctions in Xenopus cell culture (5). Will neurotrophins also serve as neuromodulators exerting fast regulation on synaptic activity in central nervous system (CNS) neurons?Neurotrophins and their receptors, the trk tyrosine kinases, are widely expressed in the brain (6-12). The fact that the expression of neurotrophins is rapidly enhanced by neuronal activity in CNS (13-22) suggests their role in activity-dependent processes, such as synaptic development and plasticity. In the present study, we sought to examine the acute effects of NT-3 on developing cortical synapses in culture, using electrophysiological approaches. We now provide direct evidence that NT-3 specifically enhances impulse activity in neurons derived from somoatosensory cortex and induces synchronization of excitatory synaptic currents. Moreover, the potentiation of neuronal activity appears to be attributable to a reduction of yaminobutyric acid (GABA)ergic synaptic transmission. Our results support the ...

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