Pyramidal cell

Abstract: How random is the discharge pattern of cortical neurons? We examined recordings from primary visual cortex (V1; Knierim and Van Essen, 1992) and extrastriate cortex (MT; Newsome et al., 1989a) of awake, behaving macaque monkey and compared them to analytical predictions. For nonbursting cells firing at sustained rates up to 300 Hz, we evaluated two indices of firing variability: the ratio of the variance to the mean for the number of action potentials evoked by a constant stimulus, and the rate-normalized coefficient of variation (Cv) of the interspike interval distribution. Firing in virtually all V1 and MT neurons was nearly consistent with a completely random process (e.g., Cv approximately 1). We tried to model this high variability by small, independent, and random EPSPs converging onto a leaky integrate-and- fire neuron (Knight, 1972). Both this and related models predicted very low firing variability (Cv << 1) for realistic EPSP depolarizations and membrane time constants. We also simulated a biophysically very detailed compartmental model of an anatomically reconstructed and physiologically characterized layer V cat pyramidal cell (Douglas et al., 1991) with passive dendrites and active soma. If independent, excitatory synaptic input fired the model cell at the high rates observed in monkey, the Cv and the variability in the number of spikes were both very low, in agreement with the integrate-and-fire models but in strong disagreement with the majority of our monkey data. The simulated cell only produced highly variable firing when Hodgkin-Huxley- like currents (INa and very strong IDR) were placed on distal dendrites. Now the simulated neuron acted more as a millisecond- resolution detector of dendritic spike coincidences than as a temporal integrator. We argue that neurons that act as temporal integrators over many synaptic inputs must fire very regularly. Only in the presence of either fast and strong dendritic nonlinearities or strong synchronization among individual synaptic events will the degree of predicted variability approach that of real cortical neurons.

Abstract: O'Keefe and Recce [1993] Hippocampus 3:317-330 described an interaction between the hippocampal theta rhythm and the spatial firing of pyramidal cells in the CA1 region of the rat hippocampus: they found that a cell's spike activity advances to earlier phases of the theta cycle as the rat passes through the cell's place field. The present study makes use of large-scale parallel recordings to clarify and extend this finding in several ways: 1) Most CA1 pyramidal cells show maximal activity at the same phase of the theta cycle. Although individual units exhibit deeper modulation, the depth of modulation of CA1 population activity is about 50%. The peak firing of inhibitory interneurons in CA1 occurs about 60 degrees in advance of the peak firing of pyramidal cells, but different interneurons vary widely in their peak phases. 2) The first spikes, as the rat enters a pyramidal cell's place field, come 90 degrees-120 degrees after the phase of maximal pyramidal cell population activity, near the phase where inhibition is least. 3) The phase advance is typically an accelerating, rather than linear, function of position within the place field. 4) These phenomena occur both on linear tracks and in two-dimensional environments where locomotion is not constrained to specific paths. 5) In two-dimensional environments, place-related firing is more spatially specific during the early part of the theta cycle than during the late part. This is also true, to a lesser extent, on a linear track. Thus, spatial selectivity waxes and wanes over the theta cycle. 6) Granule cells of the fascia dentata are also modulated by theta. The depth of modulation for the granule cell population approaches 100%, and the peak activity of the granule cell population comes about 90 degrees earlier in the theta cycle than the peak firing of CA1 pyramidal cells. 7) Granule cells, like pyramidal cells, show robust phase precession. 8) Cross-correlation analysis shows that portions of the temporal sequence of CA1 pyramidal cell place fields are replicated repeatedly within individual theta cycles, in highly compressed form. The compression ratio can be as much as 10:1. These findings indicate that phase precession is a very robust effect, distributed across the entire hippocampal population, and that it is likely to be inherited from the fascia dentata or an earlier stage in the hippocampal circuit, rather than generated intrinsically within CA1. It is hypothesized that the compression of temporal sequences of place fields within individual theta cycles permits the use of long-term potentiation for learning of sequential structure, thereby giving a temporal dimension to hippocampal memory traces.

Abstract: Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

Abstract: Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle.