These findings, RAD001 taken together with our previous bulk tracing results (Wimmer et al., 2010), indicate that such experience-dependent rewiring of the thalamocortical projection may occur in

as little as 3 days. Rapid receptive field changes in any TC-innervated layer, as recently observed for L5 (Jacob et al., 2012), may partially derive from rapid rewiring of TC anatomy. Given that interbouton distances along axons were unperturbed by trimming, our results indicate a striking reduction in the number of thalamocortical synapses. This reduction was highly unexpected because the sensory responses of single units in L4 are largely regarded as stable, whereas other layers seem robustly plastic (Feldman and Brecht, 2005, Fox, 2002 and Karmarkar and Dan, 2006). We too observed that L4 response magnitudes are

relatively stable. Our results demonstrate that single-unit recordings from a neuronal population do not necessarily allow the inference of anatomical changes among its inputs. One possible explanation is that feedforward inhibition in the thalamocortical circuit maintains L4 responsiveness in the face of TC pruning. Trimming would simultaneously decrease both feedforward excitation and inhibition, possibly leaving L4 response magnitudes unchanged. In this scenario, other functional aspects of cortical activity, beyond the magnitude of sensory-evoked responses, might be plastic. Sensory information may be robustly encoded by near-synchronous discharges of neurons rather than by uncoordinated KPT330 increases in their firing rates (reviewed in Bruno, 2011). For example, the degree of millisecond-timescale synchrony among TC neurons and consequent L4 discharges varies depending on features of whisker stimuli (Bruno and Sakmann, 2006, Temereanca et al., 2008 and Wang et al., 2010). Experience-induced reduction in TC axonal arborization in and of itself would reduce the common input shared by cortical neurons, which

in the simplest case would decrease correlated discharges among L4 neurons during sensory stimulation. Our data show, however, that reduced TC innervation does not guarantee reduced L4 synchrony, indicating that additional elements of the thalamocortical circuit are plastic. aminophylline The loss of afferent input might additionally trigger homeostatic rescaling of the strength of synapses—afferent and/or intracortical—onto an excitatory L4 neuron to maintain its normal firing rate. Consistent with this possibility, we observed that trimming enhances the strengths of common inputs shared by L4 neurons. Synaptic rescaling of intracortical connections within layer 4 is thought to switch off during development but has not yet been studied for thalamocortical connections (Turrigiano, 2011). Reduced TC innervation may directly or indirectly lead to potentiation of unpruned TC synapses.