Spike timing-dependent plasticity (STDP) is a computationally powerful form of plasticity in which synapses are strengthened or weakened according to the temporal order and precise millisecond-scale delay between presynaptic and postsynaptic spiking activity. STDP is readily observed in vitro, but evidence for STDP in vivo is scarce. Here, we studied spike timing-dependent synaptic depression in single putative pyramidal neurons of the rat primary somatosensory cortex (S1) in vivo, using two techniques. First, we recorded extracellularly from layer 2/3 (L2/3) and L5 neurons, and paired spontaneous action potentials (postsynaptic spikes) with subsequent subthreshold deflection of one whisker (to drive presynaptic afferents to the recorded neuron) to produce "post-leading-pre" spike pairings at known delays. Short delay pairings (Ͻ17 ms) resulted in a significant decrease of the extracellular spiking response specific to the paired whisker, consistent with spike timing-dependent synaptic depression. Second, in whole-cell recordings from neurons in L2/3, we paired postsynaptic spikes elicited by direct-current injection with subthreshold whisker deflection to drive presynaptic afferents to the recorded neuron at precise temporal delays. Post-leading-pre pairing (Ͻ33 ms delay) decreased the slope and amplitude of the PSP evoked by the paired whisker, whereas "pre-leading-post" delays failed to produce depression, and sometimes produced potentiation of whiskerevoked PSPs. These results demonstrate that spike timing-dependent synaptic depression occurs in S1 in vivo, and is therefore a plausible plasticity mechanism in the sensory cortex.

Summary Most functional plasticity studies in the cortex have focused on layers (L) II/III and IV, whereas relatively little is known of LV. Structural measurements of dendritic spines in vivo suggest some specialisation among LV cell subtypes. We therefore studied experience-dependent plasticity in the barrel cortex using intracellular recordings to distinguish regular spiking (RS) and intrinsic bursting (IB) subtypes. Post-synaptic potentials and suprathreshold responses in vivo revealed a remarkable dichotomy in RS and IB cell plasticity; spared whisker potentiation occurred in IB but not RS cells while deprived whisker depression occurred in RS but not IB cells. Similar RS/IB differences were found in the LII/III to V connections in brain slices. Modelling studies showed that subthreshold changes predicted the suprathreshold changes. These studies demonstrate the major functional partition of plasticity within a single cortical layer and reveal the LII/III to LV connection as a major excitatory locus of cortical plasticity.

Rats discriminate objects by scanning their surface with the facial vibrissae, producing spatiotemporally complex sequences of tactile contacts. The way in which the somatosensory cortex responds to these complex multivibrissal stimuli has not been explored. It is unclear yet whether contextual information from across the entire whisker pad influences cortical responses. Here, we delivered tactile stimuli to the rat vibrissae using a new 24 whisker stimulator. We tested sequences of rostrocaudal whisker deflections that generate multivibrissal motion patterns in different directions across the mystacial pad, allowing to disambiguate local from global sensory integration. Unitary electrophysiological recordings from different layers of the barrel cortex showed that a majority of neurons has direction selectivity for the multivibrissal stimulus. The selectivity resulted from nonlinear integration of responses across the mystacial pad. Our results indicate that the system extracts collective properties of a tactile scene.

. Spatiotemporal characteristics of neuronal sensory integration in the barrel cortex of the rat. J Neurophysiol 93: 1450 -1467, 2005. First published October 20, 2004 doi:10.1152/ jn.00912.2004. In primary sensory cortices, neuronal responses to a stimulus presented as part of a rapid sequence often differ from responses to an isolated stimulus. It has been reported that sequential stimulation of two whiskers produces facilitatory modulations of barrel cortex neuronal responses. These results are at odds with the well-known suppressive interaction that has been usually described. Herein, we have examined the dependency of response modulation on the spatiotemporal pattern of stimulation by varying the spatial arrangement of the deflected vibrissae, the temporal frequency of stimulation, and the time interval between whisker deflections. Extracellular recordings were made from primary somatosensory cortex of anesthetized rats. Two contralateral whiskers were stimulated at 0.5 and 8 Hz at intervals ranging from 0 to Ϯ30 ms. Response interactions were assessed during stimulation of the principal and adjacent whiskers, first from the same row and second from the same arc. When tested at 0.5 Hz, 59% of single units showed a statistically significant suppressive interaction, whereas response facilitation was found in only 6% of cells. In contrast, at 8 Hz, a significant supralinear summation was observed in 19% of the cells, particularly for stimulations along an arc rather than along a row. Multi-unit recordings showed similar results. These observations indicate that most of the interactions in the barrel cortex during two-whisker stimulation are suppressive. However, facilitation can be revealed when stimuli are applied at a physiological frequency and could be the basis for internal representations of the spatiotemporal pattern of the stimulus.