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Intracellular recordings were obtained from pyramidal neurons in layer 5 of rat somatosensory and visual cortical slices maintained in vitro. When directly depolarized, one subclass of pyramidal neurons had the capacity to generate intrinsic burst discharges and another generated regular trains of single spikes. Burst responses were triggered in an all-or-none manner from depolarizing afterpotentials in most bursting neurons. Regular spiking cells responded to electrical stimulation of ascending afferents with a typical EPSP-IPSP sequence, whereas IPSPs were hard to detect in bursting cells. Orthodromic activation of the latter evoked a prominent voltage-dependent depolarization that could trigger a burst response. Intracellularly labelled bursting and regular spiking cells were located in layer 5b, but had distinctly different morphologies. Bursting neurons had a large pyramidal soma, a gradually emerging apical dendrite, and an extensive apical and basal dendritic tree. Their axonal collateral arborization was predominantly limited to layers 5/6. In contrast, regular spiking cells had a more rounded soma with abruptly emerging apical dendrite, a smaller dendritic arborization, and 2 to 8 ascending axonal collaterals that arborized widely in the supragranular layers. Both bursting and regular spiking cells had main axons that entered the subcortical white matter. These data show that some subgroups of pyramidal neurons within the deeper parts of layer 5 of rat cortex are morphologically and physiologically distinct and have different intracortical connections. Bursting cells presumably function to amplify and synchronize cortical outputs, whereas regular spiking output neurons provide excitatory feedback to neurons at all cortical levels and receive a more effective orthodromic inhibitory input. These data support the hypothesis that differences in gross neuronal structure, perhaps even the subtle differences that distinguish subclasses of neurons in a given lamina, are predictive of underlying differences in the type and distribution of ion channels in the nerve cell membrane and connections of cells within the cortical circuit.

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1. The cellular mechanisms of synchronous synaptic activity were studied in isolated slices of rat SmI neocortex in which gamma-aminobutyric acid (GABA)-mediated inhibition was slightly suppressed. Intracellular measurements were made from single neurons, and extracellular recordings monitored the timing and intensity of population events. 2. Neurons in cortical layers II-VI were classified by the attributes of their single action potentials and repetitive firing patterns during injection of intracellular current pulses. Regular-spiking (RS) cells occurred in all layers and had relatively long-duration spikes and strong frequency adaptation. Intrinsically bursting (IB) cells occurred only in layers IV and V and generated bursts of greater than or equal to 3 spikes; some IB cells of lower-layer V produced repetitive bursts during long depolarizing pulses. Fast-spiking (FS) cells had brief spikes and little or no adaptation and fired at high frequencies. 3. When GABAA-mediated inhibition was slightly reduced with low doses of bicuculline methiodide (BMI, 0.8-1.0 microM), synchronous events were evoked by stimulating layer VI with single shocks. Synchronous events were characterized by prominent, often all-or-none extracellular field potentials that propagated horizontally for variable distances up to several millimeters. Large field potentials were invariably correlated with excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in single neurons. Both PSPs and field potentials often had long (up to 250 ms) and variable latencies, and sometimes two or more events were generated by single stimuli. In all cases the PSPs and field potentials were synchronous. Both field potentials and single cells sometimes generated short epochs (3-7 peaks) of rhythmic events at 20-50 Hz. 4. The physiological class of single neurons was correlated with the relative dominance of excitation and inhibition during each synchronous event. In phase with each synchronous event, most RS cells were very strongly inhibited with only small amounts of concurrent excitation. By contrast, IB cells were strongly and consistently excited, with relatively little inhibition. FS cells were also phasically excited. 5. Anatomic studies have identified RS and IB cells as pyramidal cells and FS cells as GABAergic nonpyramidal cells. This implies that, during the synchronous events of the present study, the majority of pyramidal cells were dominated by IPSPs. Synchronous excitation of FS cells, the presumed inhibitory interneurons, is consistent with this. Only a subset of the pyramidal neurons, almost all of them IB cells of the middle layers, displayed strong, synchronous excitation and clusters of action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

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1. Suppression of GABAA receptor-mediated inhibition disrupts the neural activity of neocortex and can lead to synchronized discharges that mimic those of partial epilepsy. We have studied the role of GABAA-mediated inhibition in controlling the synchronization and horizontal (tangential) spread of cortical activity. 2. Slices of rat SmI were maintained in vitro and focally stimulated in layer VI while recording with a horizontal array of extracellular electrodes. Inhibition was slightly suppressed by adding low concentrations of the GABAA antagonists bicuculline or bicuculline methiodide to the bathing medium. Under control conditions neural activity was narrowly confined to a vertical strip of cortex. The horizontal spread of activity expanded about twofold in the presence of antagonist concentrations (less than or equal to 0.5 microM) that were expected to suppress GABAA function by no more than 10-20%. 3. At antagonist concentrations between 0.4 and 1.0 microM, evoked epileptiform activity appeared. These threshold-dose epileptiform events showed wide variations in size and duration (even at the same recording site), very variable distances of horizontal propagation, specific sites of propagation failure, reversals of propagation direction, and directional asymmetries in their probability of propagation. This contrasts with activity observed previously (Ref. 9) in high bicuculline concentrations (greater than or equal to 10 microM): large, stereotyped events that propagate reliably without decrement or reflection. 4. Intracellular recordings were obtained from pyramidal neurons in layers II/III in the presence of less than or equal to 1 microM bicuculline. Inhibitory postsynaptic potentials (IPSPs) were observed during both primary evoked responses and propagating epileptiform events and were often comparable in size and duration to those in untreated cortex. Epileptiform field potentials were always correlated with synaptic activity in single cells, but the pattern and type of PSPs varied with the form of the field potentials. Large amplitude epileptiform events coincided with an overwhelming inhibition of upper layer neurons. 5. We conclude that 1) the horizontal spread of normal cortical activity is strongly constrained by GABAA-mediated IPSPs, 2) a relatively small reduction in the efficacy of inhibition leads to a large increase in the spread of excitation, 3) initiation and propagation of synchronized epileptiform activity can occur even in the presence of robust cortical inhibition, and 4) the character of epileptiform activity is strongly affected by the influences of inhibition.

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