We performed a systematic analysis of phase locking in pairs of electrically coupled neocortical fast-spiking (FS) and low-thresholdspiking (LTS) interneurons and in a conductance-based model of a pair of FS cells. Phase-response curves (PRCs) were obtained for real interneurons and the model cells. We used PRCs and the theory of weakly coupled oscillators to make predictions about phase-locking characteristics of cell pairs. Phase locking and the robustness of phase-locked states to differences in intrinsic frequencies of cells were directly examined by driving interneuron pairs through a wide range of firing frequencies.Calculations using PRCs accurately predicted that electrical coupling robustly synchronized the firing of interneurons over all frequencies studied (FS, ϳ25-80 Hz; LTS, ϳ10 -30 Hz). The synchronizing ability of electrical coupling and the robustness of the phaselocked states were directly dependent on the strength of coupling but not on firing frequency. The FS cell model also predicted the existence of stable antiphase firing at frequencies below ϳ30 Hz, but no evidence for stable antiphase firing was found using the experimentally determined PRCs or in direct measures of phase locking in pairs of interneurons. Despite significant differences in biophysical properties of FS and LTS cells, their phase-locking behavior was remarkably similar. The wide spikes and shallow action potential afterhyperpolarizations of interneurons, compared with the model, prohibited antiphase behavior. Electrical coupling between cortical interneurons of the same type maintained robust synchronous firing of cell pairs for up to ϳ10% heterogeneity in their intrinsic frequencies.

Sharp electrodes were used to record light-evoked postsynaptic potentials (PSPs) from neurons in turtle visual cortex in an in vitro preparation of the geniculocortical pathway. Neurons were placed into four groups based on the firing patterns produced by intracellular current injections: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH) cells. RS cells have been shown to be pyramidal cells while FS cells are typically interneurons. Light stimuli were diffuse, 1-s flashes of 640-nm light with intensities (I) varying from 0 to 10(4) photons microm(-2) s(-1). The response (R) in each case was the maximal amplitude of the light-evoked depolarizing PSP. Cells of all four types showed sigmoidal intensity-response (IR) functions with a linear rising phase for stimuli above the intensity threshold followed by saturation at high light intensities. Responses at high intensities were variable and some cells showed indications of supersaturation. Light-evoked PSPs had longer latencies and times-to-peak response in RS cells than they did in FS cells. RS cells fired action potentials as much as 200 ms later than did FS cells. Since responses recorded in RS cells at light intensities just above threshold are unlikely to involve contributions from other pyramidal cells, these data indicate that the geniculocortical or feedforward pathway to pyramidal cells has a high gain. The fact that FS cells fire well before RS cells suggests that feedforward inhibition plays a role in controlling the gain of the geniculocortical pathway.

Individual neurons have been shown to exhibit target cell-specific synaptic function in several brain areas. The time course of the postsynaptic conductances (PSCs) strongly influences the dynamics of local neural networks. Cartwheel cells (CWCs) are the most numerous inhibitory interneurons in the dorsal cochlear nucleus (DCN). They are excited by parallel fiber synapses, which carry polysensory information, and in turn inhibit other CWCs and the main projection neurons of the DCN, pyramidal cells (PCs). CWCs have been implicated in "context-dependent" inhibition, producing either depolarizing (other CWCs) or hyperpolarizing (PCs) post synaptic potentials. In the present study, we used paired whole cell recordings to examine target-dependent inhibition from CWCs in neonatal rat DCN slices. We found that CWC inhibitory postsynaptic potentials (IPSPs) onto PCs are large (1.3 mV) and brief (half-width = 11.8 ms), whereas CWC IPSPs onto other CWCs are small (0.2 mV) and slow (half-width = 36.8 ms). Evoked IPSPs between CWCs exhibit paired-pulse facilitation, while CWC IPSPs onto PCs exhibit paired-pulse depression. Perforated-patch recordings showed that spontaneous IPSPs in CWCs are hyperpolarizing at rest with a mean estimated reversal potential of -67 mV. Spontaneous IPSCs were smaller and lasted longer in CWCs than in PCs, suggesting that the kinetics of the receptors are different in the two cell types. These results reveal that CWCs play a dual role in the DCN. The CWC-CWC network interactions are slow and sensitive to the average rate of CWC firing, whereas the CWC-PC network is fast and sensitive to transient changes in CWC firing.

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Sensorineural hearing loss during early childhood alters auditory cortical evoked potentials in humans and profoundly changes auditory processing in hearing-impaired animals. Multiple mechanisms underlie the early postnatal establishment of cortical circuits, but one important set of developmental mechanisms relies on the neuromodulator serotonin (5-hydroxytryptamine [5-HT]). On the other hand, early sensory activity may also regulate the establishment of adultlike 5-HT receptor expression and function. We examined the role of 5-HT in auditory cortex by first investigating how 5-HT neurotransmission and 5-HT(2) receptors influence the intrinsic excitability of layer II/III pyramidal neurons in brain slices of primary auditory cortex (A1). A brief application of 5-HT (50 μM) transiently and reversibly decreased firing rates, input resistance, and spike rate adaptation in normal postnatal day 12 (P12) to P21 rats. Compared with sham-operated animals, cochlear ablation increased excitability at P12-P21, but all the effects of 5-HT, except for the decrease in adaptation, were eliminated in both sham-operated and cochlear-ablated rats. At P30-P35, cochlear ablation did not increase intrinsic excitability compared with shams, but it did prevent a pronounced decrease in excitability that appeared 10 min after 5-HT application. We also tested whether the effects on excitability were mediated by 5-HT(2) receptors. In the presence of the 5-HT(2)-receptor antagonist, ketanserin, 5-HT significantly decreased excitability compared with 5-HT or ketanserin alone in both sham-operated and cochlear-ablated P12-P21 rats. However, at P30-P35, ketanserin had no effect in sham-operated and only a modest effect cochlear-ablated animals. The 5-HT(2)-specific agonist 5-methoxy-N,N-dimethyltryptamine also had no effect at P12-P21. These results suggest that 5-HT likely regulates pyramidal cell excitability via multiple receptor subtypes with opposing effects. These data also show that early sensorineural hearing loss affects the ability of 5-HT receptor activation to modulate A1 pyramidal cell excitability.