Glutamatergic Afferents of the Ventral Tegmental Area in the Rat

Abstract

Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial to the capacity of the VTA to detect and signal stimulus salience, have been reported to arise in but a few structures. However, the afferent system of the VTA comprises very abundant neurons within a large formation extending from the prefrontal cortex to the caudal brainstem. Neurons in nearly all parts of this continuum may be glutamatergic and equivalently important to VTA function. Thus, we sought to identify the full range of glutamatergic inputs to the VTA by combining retrograde transport of wheat germ agglutinin-bound gold after injections into the VTA with nonisotopic in situ hybridization of the vesicular glutamate transporters (VGLUTs) 1, 2, and 3. We found glutamatergic neurons innervating the VTA in almost all structures projecting there and that a majority of these are subcortical and VGLUT2 mRNA positive. The tremendous convergence of glutamatergic afferents from many brain areas in the VTA suggests that (1) the function of the VTA requires integration of manifold and diverse bits of information and (2) the activity of the VTA reflects the ongoing activities of various combinations of its afferents.

Vesicular glutamate transporter 3-immunoreactive pericellular baskets ensheath a distinct population of neurons in the lateral septum

“…Despite the apparent VGLUT3-ir PBs, VGLUT3-mRNA was not expressed in LS neurons in all these studies; a finding that was recently confirmed by Geisler et al (2007). In contrast, VGLUT3-mRNA was found in deeper brain areas like hypothalamus, substantia nigra and dorsal raphe (Fremeau et al, 2002;Gras et al, 2002;Herzog et al, 2004;Schäfer et al, 2002).…”

“…These results indicate that an origin of VGLUT3-ir afferents from a deeper brainstem modulatory system is probable. The median and dorsal raphe nuclei are potent candidates for these VGLUT3-ir projections as they have been shown to be the origin of VGLUT3-positive projections to a variety of brain regions (Geisler et al, 2007;Hioki et al, 2004;Somogyi et al, 2004). Tract tracing studies will elucidate whether the VGLUT3-ir fibers originate in pure glutamatergic neurons or in neurons that co-produce another transmitter, but release the glutamate at different sites.…”

Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System

“…The VTA primarily receives excitatory neuronal input from the PFC while receiving inhibitory input from the amygdala. 132 Acute administration of morphine directly into the VTA induces release of DA in the NAc as measured by microdialysis in rats. 133 This coincides with increased firing of dopaminergic neurons in the VTA with acute IV morphine.…”

Deficient reinforcement learning in medial frontal cortex as a model of dopamine-related motivational deficits in ADHD

“…A possible answer could be that the mesolimbic pathway is also involved in executive tasks indirectly, by regulating activity in the mesocortical pathway (e.g. via ACC-to-VTA projections) (Devinsky, Morrell, & Vogt, 1995;Geisler, Derst, Veh, & Zahm, 2007) (Yu & Dayan, 2005). Hence, one can hypothesize that ACC impairments could be at least partially responsible for the executive dysfunctions in ADHD via LC dysregulation.…”