The site of impulse initiation is crucial for the integrative actions of mammalian central neurons, but this question is currently controversial. Some recent studies support classical evidence that the impulse always arises in the soma-axon hillock region, with back-propagation through excitable dendrites, whereas others indicate that the dendrites are sufficiently excitable to initiate impulses that propagate forward along the dendrite to the soma-axon hillock. This issue has been addressed in the olfactory mitral cell, in which excitatory synaptic input is restricted to the distal tuft of a single primary dendrite. In rat olfactory bulb slices, dual whole cell recordings were made at or near the soma and from distal sites on the primary dendrite. The results show that the impulse can be initiated in either the soma-axon hillock or in the distal primary dendrite, and that the initiation site is controlled physiologically by the excitatory synaptic inputs to the distal tuft and inhibitory synaptic inputs near the soma.

1. We have developed a compartmental model of a turtle cerebellar granule cell consisting of 13 compartments that represent the soma and 4 dendrites. We used this model to investigate the synaptic integration of mossy fiber inputs in granule cells. 2. The somatic compartment contained six active ionic conductances: a sodium conductance with fast activation and inactivation kinetics, gNa; a high-voltage-activated calcium conductance, gCa(HVA); a delayed potassium conductance, gK(DR); a transient potassium conductance, gK(A); a slowly relaxing mixed Na+/K+ conductance activating at hyperpolarized membrane potentials, gH, and a calcium- and voltage-dependent potassium conductance, gK(Ca). The kinetics of these conductances was derived from electrophysiological studies in a variety of preparations, including turtle and rat granule cells. 3. In the soma, dynamics of intracellular free Ca2+ was modeled by incorporation of a Na+/Ca2+ exchanger, radial diffusion, and binding sites for Ca2+. 4. The model of the turtle granule cell exhibited depolarization-induced action potential firing with properties closely resembling those seen with intracellular recordings in turtle granule cells in vitro. 5. In the most distal compartments of the dendrites, mossy fiber activity induced synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type of glutamate receptors. The strength of synaptic inputs chosen was such that the synaptic potential induced by synchronous activation of two mossy fiber synapses reached threshold for induction of a single action potential. 6. The slow time course of the NMDA synaptic current together with the slow relaxation kinetics of gH significantly affected the temporal summation of excitatory synaptic potentials. A priming action potential evoked by mossy fiber stimulation increased the maximal time interval between two synaptic potentials capable to reach again threshold for a subsequent action potential. This time interval then decreased in parallel with the decay of the NMDA synaptic current, reached a minimum after 200 ms, and slowly recovered with reactivation of gH. 7. Repetitive, steady activation of synaptic conductances by a single mossy fiber at different frequencies induced action potential firing with a sharp threshold at 12 Hz. Activity of a single or of several mossy fibers induced firing of the granule cell at a frequency close to that induced when the average synaptic current was directly injected into the cell. The mossy fiber activity-granule cell firing frequency curve was close to linear with a slope of about one-half for input frequencies < or = 400 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

SUMMARY1. The intrinsic response properties of turtle Purkinje cells and the underlying conductances have been investigated with intradendritic and intrasomatic recordings in a slice preparation.2. The active generation site for fast Na+ spikes was confined to the soma and for slow Ca2+ spikes to the dendrites. The configuration and generation of Ca2+ spikes was more affected by the level of extracellular K+ than were Na+ spikes.3. Sodium spikes had a lower threshold than Ca2+ spikes at all recording sites. Sodium spike firing was abruptly initiated during depolarizing current pulses and the spike frequency increased from an early minimum to a higher steady-state level over a period of seconds or until the occurrence of Ca21 spikes. Calcium spikes were always delayed by at least 100 ms from the onset of a depolarizing current pulse from rest.4. The abrupt onset of Na+ spike firing was due to a tetrodotoxin-sensitive plateau potential. The phase of accelerating firing frequency and the delayed occurrence of Ca2+ spikes was due to a transient hyperpolarization activated by depolarization from rest or from more negative inembrane potentials. The transient hyperpolarization was inactivated by depolarized holding potentials and was most probably generated by a rapidly inactivating K+ channel.5. It is concluded that turtle Purkinje cells display the basic firing properties and underlying conductances known from Purkinje cells of other vertebrates. In turtle Purkinje cells Ca2+ spikes are actively generated in spiny dendrites and it is suggested that spiny dendrites rather than branch points are 'hot spots'.6. The transient hyperpolarization, not previously described in Purkinje cells, seems particularly important for regulating Caa2+-dependent excitability.