To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.

Neurons in sensory systems respond to stimuli within their receptive fields, but the magnitude of the response depends on specific stimulus features. In the rodent whisker system, the response magnitude to the deflection of a particular whisker is, in most cells, dependent on the direction of deflection. Here we use in vivo intracellular recordings from thalamorecipient neurons in layers 3 and 4 of the rat barrel cortex to elucidate the dynamics of the synaptic inputs underlying direction selectivity. We show that cells are direction selective despite a broadly tuned excitatory and inhibitory synaptic input. Selectivity emerges from a direction-dependent temporal shift of excitation relative to inhibition. For preferred direction deflections, excitation precedes inhibition, but as the direction diverges from the preferred, this separation decreases. Our results illustrate a mechanism by which the timing of the synaptic inputs, and not their relative peak amplitudes, primarily determine feature selectivity.

Feature selectivity is a fundamental property of sensory cortex neurons, yet the mechanisms underlying its genesis are not fully understood. Using intracellular recordings in vivo from layers 2-6 of rat barrel cortex, we studied the selectivity of neurons to the angular direction of whisker deflection. The spike output and the underlying synaptic response decreased exponentially in magnitude as the direction of deflection diverged from the preferred. However, the spike output was more sharply tuned for direction than the underlying synaptic response amplitude. This difference in selectivity was attributable to the rectification imposed by the spike threshold on the input-output function of cells. As in the visual system, spike threshold was not constant and showed trial-to-trial variability. However, here we show that the mean spike threshold was direction dependent and increased as the direction diverged from the preferred. Spike threshold was also related to the rate of rise of the synaptic response, which was direction dependent and steepest for the preferred direction. To assess the impact of the direction-dependent changes in spike threshold on direction selectivity, we applied a fixed threshold to the synaptic responses and calculated a predicted spike output. The predicted output was more broadly tuned than the obtained spike response, demonstrating for the first time that the regulation of the spike threshold by the properties of the synaptic response effectively enhances the selectivity of the spike output.

To study the synaptic and spike responses of barrel cortex neurons as a function of cortical layer and stimulus intensity, we recorded intracellularly in vivo from barbiturate anesthetized rats while increasing the velocity-acceleration of the whisker deflection. Granular (Gr; layer 4) cells had the EPSP with the shortest peak and onset latency, whereas supragranular (SGr; layers 2-3) cells had the EPSP with longest duration and slowest rate of rise. Infragranular (Igr; layers 5-6) cells had intermediate values, and thus each layer was unique. The spike response peak of Gr cells was followed by IGr and then by SGr cells. In all cells, depolarization reduced the duration and amplitude of the response, but only in Gr cells did it reveal an early IPSP that cut short the EPSP. This early IPSP was associated with a large decrease in input resistance and an apparent reversal potential below spike threshold; consequently, synaptic integration in Gr cells was limited to the initial 5-7 msec of the response. In contrast, in SGr and IGr cells, results suggest an overlap in time of the EPSP and IPSP, with a small drop in input resistance and an apparent reversal potential above spike threshold, facilitating input integration for up to 20 msec. Decreasing stimulus intensity (velocity-acceleration) reduced the amplitude and increased the peak latency of the response without altering its synaptic composition. We propose that layer 4 circuits are better suited to perform coincidence detection, whereas supra and infragranular circuits are better designed for input integration.

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.