Braking Dopamine Systems: A New GABA Master Structure for Mesolimbic and Nigrostriatal Functions

Abstract

A new mesopontine structure exerting a strong influence on dopamine systems has been recently defined: the tail of the ventral tegmental area / rostromedial tegmental nucleus (tVTA/RMTg). This review presents a neuroanatomical, physiological and behavioral overview of some of the recent and ongoing research on this brain region and its relationship with dopamine systems. The tVTA/RMTg sends dense GABA projections to VTA and substantia nigra neurons. The inhibitory influence of tVTA/RMTg on dopamine neurons is supported by both neuroanatomical and electrophysiology data. The latter studies also reveal the tVTA/RMTg as a substrate for morphine and cannabinoid action on dopamine cells. In primates, the tVTA/RMTg has been implicated in reward prediction error signals, through a basal ganglia - lateral habenula -tVTA/RMTg - dopamine - basal ganglia circuit. In rodents, the tVTA/RMTg has been shown to play a critical role in aversive behaviors, particularly those involving behavioral inhibition, such as freezing and avoidance. These findings highlight the functional importance of the tVTA/RMTg as a major GABA brake for dopamine systems.

Differentiation and molecular heterogeneity of inhibitory and excitatory neurons associated with midbrain dopaminergic nuclei

“…11B) (Zhou and Lee, 2011;Barrot et al, 2012;Lammel et al, 2014;Morales and Root, 2014). Our current results demonstrate that these diverse GABAergic and glutamatergic neurons originate in a specific region of ventrolateral r1 and reveal a molecular framework controlling their differentiation and heterogeneity.…”

“…Collectively, these GABAergic neurons are referred to as dopaminergic neuron-associated GABAergic (D-GABA) neurons . It has been suggested that the RMTg integrates signals from different parts of the brain, including the lateral habenula (LHb), converting them into inhibitory inputs to both DA and 5-HT networks (Lavezzi and Zahm, 2011;Barrot et al, 2012;Bourdy and Barrot, 2012;Proulx et al, 2014;Sego et al, 2014).…”

Possible contributions of a novel form of synaptic plasticity inAplysiato reward, memory, and their dysfunctions in mammalian brain

“…The DA potentiation is PKA and NMDA dependent, and is also activity dependenti.e., it is greater at synapses from active CS neurons (Gurden et al 2000;Otani et al 2003;Huang et al 2004;Sun et al 2005). Finally, the VTA DA neurons also send projections to postsynaptic neurons in several brain areas, including the PFC and NAc, and receive feed forward and feedback inhibition from GABA neurons in VTA and NAc (Hyman et al 2006;Nugent et al 2007;Barrot et al 2012;Cohen et al 2012). These properties of the VTA DA neurons are similar to those of the L29 neurons in Aplysia, and therefore might account for many of the same behavioral features of learning and reward.…”

Modelling the Effect of Dorsal Raphe Serotonin Neurons on Patience for Future Rewards

“…The EP projects to the LHb [13,14] at the falling edge of the signal. The EP innervates the LHb which sends a glutamergic signal to the RMTg [15] which then inhibits the VTA [16], causing a dip in DA projections (see Fig. 3).…”