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.

Spike timing dependent plasticity (STDP) is a temporally specific extension of Hebbian associative plasticity that has tied together the timing of presynaptic inputs relative to the postsynaptic single spike. However, it is difficult to translate this mechanism to in vivo conditions where there is an abundance of presynaptic activity constantly impinging upon the dendritic tree as well as ongoing postsynaptic spiking activity that backpropagates along the dendrite. Theoretical studies have proposed that, in addition to this pre- and postsynaptic activity, a “third factor” would enable the association of specific inputs to specific outputs. Experimentally, the picture that is beginning to emerge, is that in addition to the precise timing of pre- and postsynaptic spikes, this third factor involves neuromodulators that have a distinctive influence on STDP rules. Specifically, neuromodulatory systems can influence STDP rules by acting via dopaminergic, noradrenergic, muscarinic, and nicotinic receptors. Neuromodulator actions can enable STDP induction or – by increasing or decreasing the threshold – can change the conditions for plasticity induction. Because some of the neuromodulators are also involved in reward, a link between STDP and reward-mediated learning is emerging. However, many outstanding questions concerning the relationship between neuromodulatory systems and STDP rules remain, that once solved, will help make the crucial link from timing-based synaptic plasticity rules to behaviorally based learning.

Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization ( state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized state and a depolarized state, but not all fired action potentials while in the state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the state, or in the proportion of time that the membrane potential was in the state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.

The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioral task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviorally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and outline the range of parameters where this behavior is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response which could be utilized by the animal in behavior.

Active propagation of electrical signals in C . elegans neurons requires ion channels capable of regenerating membrane potentials. Here we report regenerative depolarization of a major gustatory sensory neuron, ASEL. Whole-cell patch-clamp recordings in vivo showed supralinear depolarization of ASEL upon current injection. Furthermore, stimulation of animal’s nose with NaCl evoked all-or-none membrane depolarization in ASEL. Mutant analysis showed that EGL-19, the α1 subunit of L-type voltage-gated Ca 2+ channels, is essential for regenerative depolarization of ASEL. ASEL-specific knock-down of EGL-19 by RNAi demonstrated that EGL-19 functions in C . elegans chemotaxis along an NaCl gradient. These results demonstrate that a natural substance induces regenerative all-or-none electrical signals in dendrites, and that these signals are essential for activation of sensory neurons for chemotaxis. As in other vertebrate and invertebrate nervous systems, active information processing in dendrites occurs in C . elegans , and is necessary for adaptive behavior.