Cortical integration and representation of sensory information via receptive field (RF) organization of single neurons and functional map topography built by neuronal populations are not only a matter of excitatory divergence and convergence but are substantially controlled by diverse inhibitory systems. In this project, we will investigate how RF properties and sensory map (re-)organization of the rat barrel cortex is regulated by a particular type of GABAergic neuron, namely the parvalbumin-expressing neurons that are believed to comprise fast-spiking (FS) interneurons.
We will also investigate the importance of the activity-regulating, calcium-binding protein parvalbumin. According to their high-frequency, non-adapting firing behavior and the perisomal termination of their synapses, the PV-positive neurons are thought to control, and temporally shape, the output activity of pyramidal cells. Loss of PV-expression, or loss of PV-expressing neurons is accompanied by changes in cortical excitability (including increased susceptibility for seizures), changes in gamma oscillations and changes in short-term synaptic plasticity. FS-neurons within the barrel cortex receive thalamocortical feed-forward and pyramidal cell feed-back input within layer IV (and partly L II/III) and are thus at a cardinal position to modulate the spatial aspects of cortical RFs via lateral inhibition, and the temporal integration of activity within network (cell assembly) via recurrent inhibition.
To study the specific contribution of PV-positive neurons to cortical processing of sensory information and its use-dependent plasticity, it would be ideal if one could acutely switch off the activity of these neurons. In recent experiments we found that repetitive high-frequency stimulation, applied either by transcranial magnetic stimulation (rTMS) or by intracortical microstimulation (ICMS), initiates a fast (within 1-2 h), strong (>50%) and lasting (up to 7 days) reduction in cortical parvalbumin and in part GAD67 expression, a sign of weakened activity of these neurons. We will use these tools to acutely disturb the activity of these neurons and to investigate their contribution to receptive field structure, temporal integration of sensory activity, use-dependent plasticity of the topographic map of whisker representation in the rat barrel cortex and the associated changes in plasticity-related protein expression.