Inputs to the midbrain dopaminergic complex in the rat, with emphasis on extended amygdala‐recipient sectors

Abstract

The midbrain dopaminergic neuronal groups A8, A9, A10 and A10dc occupy, respectively, the retrorubral field (RRF), substantia nigra compacta (SNc), ventral tegmental area (VTA) and ventrolateral periaqueductal gray (PAGvl). Collectively, these structures give rise to a mixed dopaminergic and non-dopaminergic projection system that essentially permits adaptive behavior. Yet, knowledge is incomplete regarding how the afferents of these structures are organized. While the VTA is known to get numerous afferents from cortex, basal forebrain and brainstem and the SNc is widely perceived as receiving inputs mainly from the striatum, the afferents of the RRF and PAGvl have yet to be addressed comprehensively. This study was done to provide an account of those connections and seek a better understanding of how afferents might contribute to the functional interrelatedness of the VTA, SNc, RRF and PAGvl. Ventral midbrain structures received injections of retrograde tracer and resulting retrogradely labeled structures were targeted with injections of anterogradely transported Phaseolus vulgaris-leucoagglutinin. While all injections of retrograde tracer into the VTA, SNc, RRF or PAGvl produced labeling in many of a long list of structures extending from the cortex to caudal brainstem, pronounced labeling of structures comprising the central division of the extended amygdala occurred following injections that involved the RRF and PAGvl. The anterograde tracing supported this finding and, interestingly, the combination of retrograde and anterograde labeling data also confirmed reports from other groups indicating that the SNc receives robust input from many of the same structures that innervate the VTA, RRF and PAGvl.

Determination of neurotensin projections to the ventral tegmental area in mice

“…For example, FG spread to the midbrain reticular formation just above the VTA could result in the FG-labeled cells that we observed in the mouse ZI. Since the ZI projects to this midbrain reticular formation in rats, but not to the VTA (Zahm et al, 2011), it is possible that our current finding of ZI Nts projections to the VTA of mice results from such an experimental artifact (Zahm et al, 2011). This could account for the apparent ZI Nts afferents to VTA found in our mouse study, and the dearth of them previously reported from rats.…”

“…Indeed, the mouse ZI and LHA contain comparable total numbers of Nts neurons projecting to the VTA (Fig. 4), but more sparse ZI Nts projections to the VTA were observed in rats (Zahm et al, 2011). Intriguingly, a higher density of mouse Nts inputs to the VTA arise from the LHA compared to the ZI, despite equivalent total numbers of afferents observed in each site (Table 2 and Fig.…”

An update on the connections of the ventral mesencephalic dopaminergic complex

“…We previously have referred to them collectively as the ‘ventral mesencephalic dopaminergic complex’ (Zahm et al, 2011b), which herein will be shortened to, ‘midbrain DA complex’. It should be clear that the A8–10 taxonomy refers explicitly to DA neurons, whereas the VTA, SNc, RRF are brainstem structures that also contain locally and distantly projecting neurons that utilize as transmitters, either co-expressed with DA or separately, gamma-aminobutyric acid (GABA), glutamate (GLU), various neuropeptides and possibly as yet unknown compounds.…”

Glutamate Mechanisms Underlying Opiate Memories

“…NMDA-Rs within the CeA are also capable of controlling the expression of CPP, and the downstream activation of ERK is required for this effect Li et al 2008Li et al , 2011a. The CeA is an output station to midbrain targets implicated in the aversive state that accompanies opiate withdrawal, including the VTA (Zahm et al 2011) and periaqueductal gray (PAG) (Rizvi et al 1991) (Fig. 1).…”

“…1) (Zahm et al 2011). Evidence suggests that activity within the CeA and BNST during protracted withdrawal may produce a "stress-like" state that can precipitate relapse (Nakagawa et al 2005b;Harris and Aston-Jones 2007).…”