SummaryThe basal ganglia are involved in sensorimotor functions and action selection, both of which require the integration of sensory information. In order to determine how such sensory inputs are integrated, we obtained whole-cell recordings in mouse dorsal striatum during presentation of tactile and visual stimuli. All recorded neurons responded to bilateral whisker stimulation, and a subpopulation also responded to visual stimulation. Neurons responding to both visual and tactile stimuli were located in dorsomedial striatum, whereas those responding only to whisker deflections were located dorsolaterally. Responses were mediated by overlapping excitation and inhibition, with excitation onset preceding that of inhibition by several milliseconds. Responses differed according to the type of neuron, with direct pathway MSNs having larger responses and longer latencies between ipsilateral and contralateral responses than indirect pathway MSNs. Our results suggest that striatum acts as a sensory “hub” with specialized functional roles for the different neuron types.

The balance between excitation and inhibition is critical in the physiology of the cerebral cortex. To understand the influence of inhibitory control on the emergent activity of the cortical network, inhibition was progressively blocked in a slice preparation that generates spontaneous rhythmic up states at a similar frequency to those occurring in vivo during slow-wave sleep or anesthesia. Progressive removal of inhibition induced a parametric shortening of up state duration and elongation of the down states, the frequency of oscillations decaying. Concurrently, a gradual increase in the network firing rate during up states occurred. The slope of transitions between up and down states was quantified for different levels of inhibition. The slope of upward transitions reflects the recruitment of the local network and was progressively increased when inhibition was decreased, whereas the speed of activity propagation became faster. Removal of inhibition eventually resulted in epileptiform activity. Whereas gradual reduction of inhibition induced linear changes in up/down states and their propagation, epileptiform activity was the result of a nonlinear transformation. A computational network model showed that strong recurrence plus activity-dependent hyperpolarizing currents were sufficient to account for the observed up state modulations and predicted an increase in activity-dependent hyperpolarization following up states when inhibition was decreased, which was confirmed experimentally.

High-frequency oscillations in cortical networks have been linked to a variety of cognitive and perceptual processes. They have also been recorded in small cortical slices in vitro, indicating that neuronal synchronization at these frequencies is generated in the local cortical circuit. However, in vitro experiments have hitherto necessitated exogenous pharmacological or electrical stimulation to generate robust synchronized activity in the ␤/␥ range. Here, we demonstrate that the isolated cortical microcircuitry generates ␤ and ␥ oscillations spontaneously in the absence of externally applied neuromodulators or synaptic agonists. We show this in a spontaneously active slice preparation that engages in slow oscillatory activity similar to activity during slow-wave sleep. ␤ and ␥ synchronization appeared during the up states of the slow oscillation. Simultaneous intracellular and extracellular recordings revealed synchronization between the timing of incoming synaptic events and population activity. This rhythm was mechanistically similar to pharmacologically induced ␥ rhythms, as it also included sparse, irregular firing of neurons within the population oscillation, predominant involvement of inhibitory neurons, and a decrease of oscillation frequency after barbiturate application. Finally, we show in a computer model how a synaptic loop between excitatory and inhibitory neurons can explain the emergence of both the slow (Ͻ1 Hz) and the ␤-range oscillations in the neocortical network. We therefore conclude that oscillations in the ␤/␥ range that share mechanisms with activity reported in vivo or in pharmacologically activated in vitro preparations can be generated during slow oscillatory activity in the local cortical circuit, even without exogenous pharmacological or electrical stimulation.

Repetitive stimulation of synaptic connections in the cerebral cortex often induces short-term synaptic depression (STD), a property directly related to the probability of transmitter release and critical for the computational properties of the network. In order to explore how spontaneous activity in the network affects this property, we first studied STD in cortical slices that were either silent or that displayed spontaneous rhythmic slow oscillations resembling those recorded during slow wave sleep in vivo. STD was considerably reduced by the occurrence of spontaneous rhythmic activity in the cortical network. Once the rhythmic activity started, depression decreased over time in parallel with the duration and intensity of the ongoing activity until a plateau was reached. Thalamocortical and intracortical synaptic potentials studied in vivo also showed stronger depression in a silent than in an active cortical network, and the depression values in the active cortical network in vivo were indistinguishable from those found in active slices in vitro. We suggest that this phenomenon is due to the different steady states of the synapses in active and in silent networks.

Reig R, Mattia M, Compte A, Belmonte C, Sanchez-Vives MV. Temperature modulation of slow and fast cortical rhythms. J Neurophysiol 103: 1253-1261, 2010. First published December 23, 2009 doi:10.1152/jn.00890.2009. In the local cortical network, spontaneous emergent activity self-organizes in rhythmic patterns. These rhythms include a slow one (Ͻ1 Hz), consisting in alternation of up and down states, and also faster rhythms (10 -80 Hz) generated during up states. Varying the temperature in the bath between 26 and 41°C resulted in a strong modulation of the emergent network activity. Up states became shorter for warmer temperatures and longer with cooling, whereas down states were shortest at physiological (36 -37°C) temperature. The firing rate during up states was robustly modulated by temperature, increasing with higher temperatures. The sparse firing rate during down states hardly varied with temperature, thus resulting in a progressive merging of up and down states for temperatures around 30°C. Below 30°C and down to 26°C the firing lost rhythmicity, becoming progressively continuous. The slope of the down-to-up transitions, which reflects the speed of recruitment of the local network, was progressively steeper for higher temperatures, whereas wave-propagation speed exhibited only a moderate increase. Fast rhythms were particularly sensitive to temperature. Broadband highfrequency fluctuations in the local field potential were maximal for recordings at 36 -38°C. Overall, we found that maintaining cortical slices at physiological temperature is critical for the generated activity to be analogous to that in vivo. We also demonstrate that changes in activity with temperature were not secondary to oxygenation changes. Temperature variation sets the in vitro cortical network at different functional regimes, allowing the exploration of network activity generation and control mechanisms.