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Stimulation of the mediodorsal and midline thalamic nuclei excites cortical neurons and induces c-fos expression in the prefrontal cortex. Data in the literature data suggest that pyramidal neurons are the most likely cellular targets. In order to determine whether cortical interneurons are also impacted by activation of mediodorsal/midline thalamic nuclei, we studied the effects of thalamic stimulation on (1) Fos protein expression in gamma-aminobutyric acid (GABA)-immunoreactive neurons and on (2) extracellular GABA levels in the prefrontal cortex of rats.. Perfusion of the GABA-A receptor antagonist bicuculline for 20 minutes through a dialysis probe implanted into the mediodorsal thalamus induced Fos-like immunoreactivity (IR) approximately 1 hour later in the thalamus and in the medial prefrontal cortex of freely moving rats. Immunohistochemical double-labeling for Fos-like IR and GABA-like IR showed that about 8% of Fos-like IR nuclei in the prelimbic and infralimbic areas were located in GABA-like LR neurons. Fos-like IR was detected in three major subsets of GABAergic neurons defined by calbindin, parvalbumin, or vasoactive intestinal peptide (VIP)-like IR. Dual probe dialysis showed that the extracellular levels of GABA in the prefrontal cortex did not change in response to thalamic stimulation. These data indicate that activation of thalamocortical neurons indeed affects the activity of GABAergic neurons as shown by the induction of Fos-like IR but that these metabolic changes are not reflected in changes of extracellular GABA levels that are sampled by microdialysis. Synapse 30:156-165, 1998. (C) 1998 Wiley-Liss, Inc.

Stimulation of the mediodorsal and midline thalamic nuclei excites cortical neurons and induces c-fos expression in the prefrontal cortex. Data in the literature data suggest that pyramidal neurons are the most likely cellular targets. In order to determine whether cortical interneurons are also impacted by activation of mediodorsal/midline thalamic nuclei, we studied the effects of thalamic stimulation on (1) Fos protein expression in gamma-aminobutyric acid (GABA)-immunoreactive neurons and on (2) extracellular GABA levels in the prefrontal cortex of rats.. Perfusion of the GABA-A receptor antagonist bicuculline for 20 minutes through a dialysis probe implanted into the mediodorsal thalamus induced Fos-like immunoreactivity (IR) approximately 1 hour later in the thalamus and in the medial prefrontal cortex of freely moving rats. Immunohistochemical double-labeling for Fos-like IR and GABA-like IR showed that about 8% of Fos-like IR nuclei in the prelimbic and infralimbic areas were located in GABA-like LR neurons. Fos-like IR was detected in three major subsets of GABAergic neurons defined by calbindin, parvalbumin, or vasoactive intestinal peptide (VIP)-like IR. Dual probe dialysis showed that the extracellular levels of GABA in the prefrontal cortex did not change in response to thalamic stimulation. These data indicate that activation of thalamocortical neurons indeed affects the activity of GABAergic neurons as shown by the induction of Fos-like IR but that these metabolic changes are not reflected in changes of extracellular GABA levels that are sampled by microdialysis. Synapse 30:156-165, 1998. (C) 1998 Wiley-Liss, Inc.

Avermann M, Tomm C, Mateo C, Gerstner W, Petersen CC. Microcircuits of excitatory and inhibitory neurons in layer 2/3 of mouse barrel cortex. J Neurophysiol 107: 3116-3134, 2012. First published March 7, 2012; doi:10.1152/jn.00917.2011.-Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo.