1. The membrane currents evoked by afferent fiber stimulation in the piriform cortex were derived by the use of current source-density (CSD) analysis in the rat under urethan anesthesia. The primary goals were to test hypotheses concerning the sequence of synaptic events evoked by afferent fiber stimulation and to derive data required for development and testing of the model presented in the companion paper. 2. In confirmation of previous studies, it was found that afferent fiber stimulation evokes a monosynaptic excitatory postsynaptic current (EPSC) in distal segments of pyramidal cell apical dendrites (layer Ia) followed by a strong disynaptic EPSC in adjacent middle segments (superficial layer Ib). 3. Given the central importance of the strong disynaptic EPSC in models for operation of the piriform cortex, the hypothesis that it is mediated by long association fibers from the anterior piriform cortex was tested by comparing its latency in response to stimulation at anterior and posterior locations. The results confirmed the hypothesis and ruled out a significant contribution from local connections in the posterior piriform cortex. 4. Intensification of pyramidal cell activity by spatially restricted disinhibition with picrotoxin confirmed the hypothesis that associational projections from the posterior piriform cortex can mediate a long-latency disynaptic EPSC in proximal dendritic segments (mid to deep layer Ib) in the anterior piriform cortex. 5. Analysis of the time course of the monosynaptic EPSC in different areas revealed that activation of the anterior piriform cortex from afferent fiber stimulation is fast and nearly synchronous throughout its extent as a result of the relatively high conduction velocities of afferent fibers in the lateral olfactory tract (LOT). By contrast, the posterior piriform cortex is sequentially activated by this EPSC as a consequence of the slow propagation velocity of afferent fiber collaterals that course across its surface. This activation is sufficiently slow that a large phase lag is present between rostral and caudal regions. 6. The time courses of the monosynaptic and principal disynaptic EPSCs changed in characteristically different ways with increasing distance from the LOT within the posterior piriform cortex. Simulations in the companion paper indicate that initiation and propagation patterns for activity in fiber systems rather than differences in synaptic conductance waveforms are responsible for these differences. 7. Although the laminar distribution of the active inward current component of the monosynaptic EPSC remained constant over time, the peak outward current associated with this EPSC shifted from the depth of proximal apical dendrites (layer Ib) to the depth of superficial pyramidal cell somata (layer II).(ABSTRACT TRUNCATED AT 400 WORDS)

Prominent, odor-evoked, fast (40-60 Hz) oscillations have been reported in the olfactory bulb and piriform (primary olfactory) cortex of both awake-behaving and anesthetized animals. The present study used current source-density analysis to examine the origin of the fast oscillations evoked by single weak shocks to afferent fibers. These shock-evoked oscillations closely resemble those evoked by odor. The results revealed that each cycle of the oscillatory field potential was generated by a stereotyped series of membrane currents similar to those previously characterized in the nonoscillatory response to strong afferent fiber shocks. Each cycle began with a strong inward current in layer la identified as an EPSC mediated by afferent fibers in distal apical dendrites of pyramidal cells. This afferent input was followed by a strong inward current in layer Ib identified as an EPSC mediated by intrinsic association fibers in middle apical dendritic segments. These excitatory events were followed by a smaller inward current at the depth of pyramidal cell somata (layers II and superficial III) that may be the depolarizing Cl(-)-mediated IPSC previously identified in the strong-shock response. Based on an analysis of the timing of the EPSCs it was concluded that the weak shock-evoked oscillation is generated in the olfactory bulb and that the resulting periodic activity in afferent fibers drives the oscillation in the piriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of the NMDA component of EPSPs by different components of postsynaptic GABAergic inhibition: computer simulation analysis in piriform cortex. J. Neurophysiol. 78: 2546-2559, 1997. Physiological analysis in the companion paper demonstrated that gamma-aminobutyric acid-A (GABAA)-mediated inhibition in piriform cortex is generated by circuits that are largely independent in apical dendritic and somatic regions of pyramidal cells and that GABAA-mediated inhibitory postsynaptic currents (IPSCs) in distal dendrites have a slower time course than those in the somatic region. This study used modeling methods to explore these characteristics of GABAA-mediated inhibition with respect to regulation of the N-methyl--aspartate (NMDA) component of excitatory postsynaptic potentials. Such regulation is relevant to understanding NMDA-dependent long-term potentiation (LTP) and the integration of repetitive synaptic inputs that can activate the NMDA component as well as pathological processes that can be activated by overexpression of the NMDA component. A working hypothesis was that the independence and differing properties of IPSCs in apical dendritic and somatic regions provide a means whereby the NMDA component and other dendritic processes can be controlled by way of GABAergic tone without substantially altering system excitability. The analysis was performed on a branched compartmental model of a pyramidal cell in piriform cortex constructed with physiological and anatomic data derived by whole cell patch recording. Simulations with the model revealed that NMDA expression is more effectively blocked by the slow GABAA component than the fast. Because the slow component is present in greater proportion in apical dendritic than somatic regions, this characteristic would increase the capacity of dendritic IPSCs to regulate NMDA-mediated processes. The simulations further revealed that somatic-region GABAergic inhibition can regulate the generation of action potentials with little effect on the NMDA component generated by afferent fibers in apical dendrites. As a result, if expression of the NMDA component or other dendritic processes were enabled by selective block of dendritic inhibition, for example, by centrifugal fiber systems that may regulate learning and memory, the somatic-region IPSC could preserve system stability through feedback regulation of firing without counteracting the effect of the dendritic-region block. Simulations with paired inputs revealed that the dendritic GABAA-mediated IPSC can regulate the extent to which a strong excitatory input facilitates the NMDA component of a concurrent weak input, providing a possible mechanism for control of "associative LTP" that has been demonstrated in this system. Postsynaptic GABAB-mediated inhibition had less effect on the NMDA component than either the fast or slow GABAA components. Depolarization from a concomitant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component also was found to have comparatively little effect on current through...

1. The detailed visualization of membrane currents over time and depth provided by current source-density (CSD) analysis was used as the basis for development of a system model that reproduces the response of piriform cortex to afferent fiber stimulation. This model has allowed the testing and substantial revision of previous hypotheses concerning the sequence of neuronal events underlying this response, has enabled net membrane currents visualized by CSD analysis to be separated into active and passive components, and has generated predictions for important axonal and synaptic parameters as well as for the behavior of piriform cortex as a system. 2. The model was developed in three steps. Activity in excitatory fiber systems was first represented with continuous distributions. The "population conductances" due to the activation of excitatory fiber systems were then computed from the distribution of action-potential arrival times and the conductance waveform for excitatory synapses. Finally, these temporally dispersed excitatory conductances and locally mediated inhibitory conductances were introduced at appropriate locations on a compartmentalized cable that simulated the passive response of the pyramidal cell population. 3. After the simulation of membrane currents at one site, all parameters in the model were fixed so that it could be used to predict the variation in the time course of membrane currents at additional recording sites; comparison with the results of CSD analysis at these sites provided the primary validation of the model. Additional validation included the simulation of membrane potentials derived by intracellular recording, including the effects of manipulating somatic potential with current injection. 4. Several conclusions have emerged from the mathematical description of activity in fiber systems. Propagation of activity in both afferent and association (corticocortical) fiber systems is "dispersive" as a result of a wide spectrum of axon conduction velocities. The characteristically different time courses of afferent and association fiber-mediated responses are largely determined by the focal, shock-evoked origin of the volley in afferent fibers as opposed to the spatially distributed disynaptic origin of activity in association fibers. Conduction velocity distributions for afferent and association fiber systems are skewed and can be approximated with lognormal distributions. 5. General solutions, which relate an arbitrary conduction velocity distribution to arrival time and spatial distributions of action potentials, were used to generate specific solutions describing the effects of dispersive propagation.(ABSTRACT TRUNCATED AT 400 WORDS)