The spiny projection neurons are by far the most numerous type of striatal neuron. In addition to being the principal projection neurons of the striatum, the spiny projection neurons also have an extensive network of local axon collaterals by which they make synaptic connections with other striatal projection neurons. However, up to now there has been no direct physiological evidence for functional inhibitory interactions between spiny projection neurons. Here we present new evidence that striatal projection neurons are interconnected by functional inhibitory synapses. To examine the physiological properties of unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings were made from pairs of spiny projection neurons in brain slices of adult rat striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using averages of 200 traces that were triggered by a single presynaptic action potential. In all cases, synaptic interactions were unidirectional, and no bidirectional interactions were detected. Unitary IPSPs evoked by a single presynaptic action potential had a peak amplitude ranging from 157 to 319 microV in different connections (mean: 277 +/- 46 microV, n = 9). The percentage of failures of single action potentials to evoke a unitary IPSP was estimated and ranged from 9 to 63% (mean: 38 +/- 14%, n = 9). Unitary IPSPs were reversibly blocked by bicuculline (n = 4) and had a reversal potential of -62.4 +/- 0.7 mV (n = 5), consistent with GABA-mediated inhibition. The findings of the present study correlate very well with anatomical evidence for local synaptic connectivity between spiny projection neurons and suggest that lateral inhibition plays a significant role in the information processing operations of the striatum.

We have used computer simulations as one way to test the hypothesis that locomotor rhythm production for swimming in frog embryo spinal cord depends on rebound from inhibition and is sustained by mutual re-excitation among spinal excitatory interneurons. All simulations were based on physiological and anatomical data on the neurons and circuitry of Xenopus embryo spinal cord. Model 'neurons' had resistively coupled axon, soma, and dendrite compartments. Membrane properties were based on Hodgkin - Huxley equations with resting potential at - 75 mV and where soma and dendrite had reduced K+ and Na+ conductance and slowed K+ conductance. These 'neurons' fired a single non-overshooting spike both to depolarizing current and after hyperpolarizing current given during imposed depolarization. Synapses were made on to the dendrite. Inhibitory and excitatory synaptic channels had Nernst potentials of - 80 and 0 mV, time constants for opening of 1 ms, and closing of 6 and 75 ms. When the short inhibitory postsynaptic potential occurred on the long (N-methyl-D-aspartate-type) excitatory postsynaptic potential, it led to rebound firing. A four 'neuron' symmetrical network was built with reciprocal inhibition and where excitatory 'neurons' re-excited themselves and the inhibitory 'neuron' on their own side. The rhythmic alternating activity with one spike per cycle produced reliably by this network was self-sustaining, initiated by a brief synaptic input, and closely resembled the spinal cord motor pattern during swimming. The robustness of this activity pattern was investigated by varying cellular and synaptic parameters, initiating inputs, and network connectivity. We conclude that cellular, synaptic, and network properties are all important and that mutual re-excitation, a form of positive feedback, could sustain motor rhythm production in the Xenopus embryo spinal cord.

1. The effect of salicylate on membrane capacitance and intracellular pH has been measured in isolated outer hair cells (OHCs) during whole cell recording. Cell membrane capacitance was measured using a lock-in amplifier technique. 2. Salicylate applied in the bath reduced the fast charge movement, equivalent to a voltagedependent membrane capacitance, present in OHCs. Simultaneous measurement of membrane capacitance and voltage-driven cell length changes showed that salicylate reduced both together. 3. A small effect of salicylate on outward currents at 0 mV was observed. Sodium salicylate (5 mM) reduced the currents by 19% and another weak acid, sodium butyrate (10 mM), reduced outward currents in OHCs by 15%. 4. The ratiometric dye 2,7-bis(2-carboxymethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pH, changes in OHCs during weak acid exposure. Membrane capacitance and pH1were measured simultaneously in OHCs exposed first to 10 mm sodium butyrate and then to 5 mM sodium salicylate. Although both compounds produced a similar reduction in pH1, butyrate decreased the resting capacitance from a mean resting capacitance of 35 pF (at -30 mV) by 5±4 + 2-1 pF, whereas salicylate decreased it by 15-7 + 2-3 pF (n = 4). 5. Exposure of OHCs to 10 mm sodium benzoate, an amphiphilic anion, reduced resting membrane capacitance at -30 mV by 9-2 + 3-2 pF (n = 3). Outward currents, measured at 0 mV, were reduced by 0-25 + 0 05 nA during benzoate application, comparable with the effect of salicylate.6. Capacitance was measured during slow bath application of salicylate. The resulting dose-capacitance curve had a Hill coefficient of 3 40 + 0-85 (n = 4) and a half-maximal dose of 3.95 + 0 34 mm. The dose-capacitance curve was not significantly voltage dependent. 7. Salicylate had no detectable effect on the resting capacitance of Deiters' cells, a non-sensory cell type of the organ of Corti. 8. It is concluded that many of the described effects of salicylate on hearing may arise from the partitioning of the salicylate molecule into the membrane of the OHC and consequent inhibition of OHC motility.

1. Intersegmental co-ordination in Xenopus embryos could be influenced by longitudinal gradients in neuronal properties or synaptic drive. To determine if such gradients exist intracellular recordings were made from putative motoneurones at different spinal levels. 2. No evidence was found of a longitudinal gradient in neuronal resting potentials. In a rostrocaudal direction the duration of current-evoked spikes increased and the amplitude of the spike after-hyperpolarization (AHP) decreased. 3. During fictive swimming the amplitude of the tonic excitatory synaptic input and the mid-cycle IPSPs declined in a rostrocaudal direction. The rise-time and fall-time of midcycle IPSPs increased in a rostrocaudal direction. 4. Rostral to the eighth post-otic segment mid-cycle IPSPs occurred on all cycles of fictive swimming episodes. More caudally IPSPs became irregular in occurrence and caudal to the twelfth post-otic segment no mid-cycle IPSPs could be detected, even during the injection of depolarizing current or when recording with KCl-filled electrodes. 5. The duration of spikes occurring during fictive swimming increased and the amplitude of spike AHP decreased in a rostrocaudal direction. A spike AHP was absent during fictive swimming activity in neurones caudal to the ninth post-otic segment even though it was present in current-evoked spikes in the same neurones. 6. On-cycle IPSPs (occurring shortly after the spike at phase values less than 04) were observed predominantly at the beginning of swimming episodes in neurones recorded rostral to the eighth segment, but were not detected at all in more caudal neurones. 7. If the rostrocaudal gradients in synaptic excitatory and inhibitory drive to putative motoneurones during fictive swimming are also present in premotor spinal interneurones they would be expected to have a strong influence on rostrocaudal delays. Such gradients could therefore be important components of the mechanism underlying intersegmental co-ordination.

This research examines the mechanisms that initiate rhythmic activity in the episodic central pattern generator (CPG) underlying escape swimming in the gastropod mollusk Tritonia diomedea. Activation of the network is triggered by extrinsic excitatory input but also accompanied by intrinsic neuromodulation and the recruitment of additional excitation into the circuit. To examine how these factors influence circuit activation, a detailed simulation of the unmodulated CPG network was constructed from an extensive set of physiological measurements. In this model, extrinsic input alone is insufficient to initiate rhythmic activity, confirming that additional processes are involved in circuit activation. However, incorporating known neuromodulatory and polysynaptic effects into the model still failed to enable rhythmic activity, suggesting that additional circuit features are also required. To delineate the additional activation requirements, a large-scale parameter-space analysis was conducted (~2 x 10(6) configurations). The results suggest that initiation of the swim motor pattern requires substantial reconfiguration at multiple sites within the network, especially to recruit ventral swim interneuron-B (VSI) activity and increase coupling between the dorsal swim interneurons (DSIs) and cerebral neuron 2 (C2) coupling. Within the parameter space examined, we observed a tendency for rhythmic activity to be spontaneous and self-sustaining. This suggests that initiation of episodic rhythmic activity may involve temporarily restructuring a nonrhythmic network into a persistent oscillator. In particular, the time course of neuromodulatory effects may control both activation and termination of rhythmic bursting.