1. We have developed a 19-compartment cable model of a guinea pig CA3 pyramidal neuron. Each compartment is allowed to contain six active ionic conductances: gNa, gCa, gK(DR) (where DR stands for delayed rectifier), gK(A), gK(AHP), and gK(C). THe conductance gCa is of the high-voltage activated type. The model kinetics for the first five of these conductances incorporate voltage-clamp data obtained from isolated hippocampal pyramidal neurons. The kinetics of gK(C) are based on data from bullfrog sympathetic neurons. The time constant for decay of submembrane calcium derives from optical imaging of Ca signals in Purkinje cell dendrites. 2. To construct the model from available voltage-clamp data, we first reproduced current-clamp records from a model isolated neuron (soma plus proximal dendrites). We next assumed that ionic channel kinetics in the dendrites were the same as in the soma. In accord with dendritic recordings and calcium-imaging data, we also assumed that significant gCa occurs in dendrites. We then attached sections of basilar and apical dendritic cable. By trial and error, we found a distribution (not necessarily unique) of ionic conductance densities that was consistent with current-clamp records from the soma and dendrites of whole neurons and from isolated apical dendrites. 3. The resulting model reproduces the Ca(2+)-dependent spike depolarizing afterpotential (DAP) recorded after a stimulus subthreshold for burst elicitation. 4. The model also reproduces the behavior of CA3 pyramidal neurons injected with increasing somatic depolarizing currents: low-frequency (0.3-1.0 Hz) rhythmic bursting for small currents, with burst frequency increasing with current magnitude; then more irregular bursts followed by afterhyperpolarizations (AHPs) interspersed with brief bursts without AHPs; and finally, rhythmic action potentials without bursts. 5. The model predicts the existence of still another firing pattern during tonic depolarizing dendritic stimulation: brief bursts at less than 1 to approximately 12 Hz, a pattern not observed during somatic stimulation. These bursts correspond to rhythmic dendritic calcium spikes. 6. The model CA3 pyramidal neuron can be made to resemble functionally a CA1 pyramidal neuron by increasing gK(DR) and decreasing dendritic gCa and gK(C). Specifically, after these alterations, tonic depolarization of the soma leads to adapting repetitive firing, whereas stimulation of the distal dendrites leads to bursting. 7. A critical set of parameters concerns the regulation of the pool of intracellular [Ca2+] that interacts with membrane channels (gK(C) and gK(AHP)), particularly in the dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Interictal spikes are a simple kind of epileptic neuronal activity. Field potentials and intracellular recordings observed during interictal spikes of penicillin-treated slices of the hippocampus were reproduced by a mathematical model of a network of 100 hippocampal neurons from the region including CA2 and CA3. The model shows that this form of neuronal synchronization arises because of mutual excitation between neurons, each of which is capable of intrinsic bursting in response to a brief input.

SUMMARY1. Excitatory synaptic interactions between CA3 neurones in slices from guinea-pig hippocampus were examined. Recurrent excitatory post-synaptic potentials (e.p.s.p.s) were evoked by action potentials in a single presynaptic neurone or by the antidromic activation of part of the CA3 pyramidal cell population.2. The peak amplitude of unitary e.p.s.p.s was 1-2 mV at potentials between -64 and -70 mV. Their time to peak was 7-12 ms and the initial phase of their decay was slower than that of a somatically injected voltage pulse. Recurrent e.p.s.p.s were often followed by a small (0-3 mV) hyperpolarization, or undershoot.

Summary Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for treatment of high cholesterol, can correct excess hippocampal protein synthesis in themouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying, and could be a viable prophylactic treatment for epileptogenesis in FXS.