Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: a combined retrograde tracing in situ hybridization study [corrected].

Glutamate transmission is critical for controlling cortical activity, but the specific contribution of the different isoforms of vesicular glutamate transporters in subcortical pathways to the neocortex is largely unknown. To determine the distribution and neocortical projections of vesicular glutamate transporter2 (Vglut2)-containing neurons, we used in situ hybridization and injections of the retrograde tracer Fluoro-Gold into the medial prefrontal and primary somatosensory cortices. The thalamus contains the majority of Vglut2 cells projecting to the neocortex (approximately 90% for the medial prefrontal cortex and 96% for the primary somatosensory cortex) followed by the hypothalamus and basal forebrain, the claustrum, and the brainstem. There are significantly more Vglut2 neurons projecting to the medial prefrontal cortex than to the primary somatosensory cortex. The medial prefrontal cortex also receives a higher percentage of Vglut2 projection from the hypothalamus than the primary somatosensory cortex. About 50% of thalamic Vglut2 projection to the medial prefrontal cortex and as much as 80% of the thalamic projection to primary somatosensory cortex originate in various relay thalamic nuclei. The remainder arise from different midline and intralaminar nuclei traditionally thought to provide nonspecific or diffuse projection to the cortex. The extrathalamic Vglut2 corticopetal projections, together with the thalamic intralaminar-midline Vglut2 corticopetal projections, may participate in diffuse activation of the neocortex.