Projections from the Rat Prefrontal Cortex to the Ventral Tegmental Area: Target Specificity in the Synaptic Associations with Mesoaccumbens and Mesocortical Neurons

By David B. Carr, S. Sesack. Journal of Neuroscience, 2000

919 citations recorded by the source corpus.

Excitatory projections from the prefrontal cortex (PFC) to the ventral tegmental area (VTA) play an important role in regulating the activity of VTA neurons and the extracellular levels of dopamine (DA) within forebrain regions. Previous investigations have demonstrated that PFC terminals synapse on the dendrites of DA and non-DA neurons in the VTA. However, the projection targets of these cells are not known. To address whether PFC afferents innervate different populations of VTA neurons that project to the nucleus accumbens (NAc) or to the PFC, a triple labeling method was used that combined peroxidase markers for anterograde and retrograde tract-tracing with pre-embedding immunogold–silver labeling for either tyrosine hydroxylase (TH) or GABA. Within the VTA, PFC terminals formed asymmetric synapses onto dendritic shafts that were immunoreactive for either TH or GABA. PFC terminals also synapsed on VTA dendrites that were retrogradely labeled from the NAc or the PFC. Dendrites retrogradely labeled from the NAc and postsynaptic to PFC afferents were sometimes immunoreactive for GABA but were never TH-labeled. Conversely, dendrites retrogradely labeled from the PFC and postsynaptic to PFC afferents were sometimes immunoreactive for TH but were never GABA-labeled. These results provide the first demonstration of PFC afferents synapsing on identified cell populations in the VTA and indicate a considerable degree of specificity in the targets of the PFC projection. The unexpected finding of selective PFC synaptic input to GABA-containing mesoaccumbens neurons and DA-containing mesocortical neurons suggests novel mechanisms through which the PFC can influence the activity of ascending DA and GABA projections.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d981d8be13845d933306547a884fba3ec2f81c1e

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Citations in the corpus

Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring (2009, background): “Summarized briefly, this model starts from the results of basic neuroanatomical and neurophysiological studies, which, as explained above, show that the activity of DAergic midbrain neurons is controlled by glutamatergic projections from prefrontal cortex.(87,88,92) These prefrontal projections are ”
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input–Output Mapping (2015, background): “Previous studies have sought to separately identify either the sources of synaptic inputs to VTA neurons (Phillipson, 1979; Carr and Sesack, 2000; Zahm et al., 2011; Watabe-Uchida et al., 2012) or the projection targets of these cells (Beckstead et al., 1979; Swanson, 1982).”
A neurobehavioral model of affiliative bonding: implications for conceptualizing a human trait of affiliation. (2005, background): “American Journal of Medical Genetics 124A:263–73. [AT] Drago, F., Caldwell, J., Pedersen, C., Continella, G., Scapagnini, U. & Prange, A. (1986) Dopamine neurotransmission in the nucleus accumbens may be involved in oxytocin-enhanced grooming behavior of the rat. Pharmacology, Biochemistry and Behav”
Synaptic plasticity and addiction (2007, background): “For example, excitatory inputs from the PFC selectively form synapses onto VTA dopaminergic neurons that project back to the PFC but not onto neighbouring dopaminergic cells in the VTA that project to the NA”
Cortico-Basal Ganglia Reward Network: Microcircuitry (2009, positive): “Ultrastructural tract-tracing indicates that PFC axons synapse onto DA neurons that project back to the PFC, creating a circuit that allows the PFC to regulate the extent of its modulatory feedback by DA (Carr and Sesack, 2000b).”
Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. (2008, positive): “In addition, insights into differences in synaptic connectivity (Carr et al., 1999; Carr and Sesack, 2000) and plasticity (Martin et al.”
The Vertebrate mesolimbic reward system and social behavior network: A comparative synthesis (2011, background): “…1981; Kelley et al., 1982; Eberhart et al., 1985; Haber et al., 1985; Yang and Mogenson, 1985; Caffe et al., 1987; Domesick, 1988; Groenewegen et al., 1993; Canteras et al., 1994; Napier et al., 1995; Numan and Numan, 1996; Pikkarainen et al., 1999; Carr and Sesack, 2000; Morgane et al., 2005.”
Whole-brain mapping of direct inputs to midbrain dopamine neurons. (2012, positive): “Electron microscopy can resolve several of these issues (e.g., Bolam and Smith, 1990; Carr and Sesack, 2000; Omelchenko et al., 2009; Omelchenko and Sesack, 2010; Somogyi et al., 1981), but this technique is not suitable for a comprehensive identification of inputs.”
Psychomotor Stimulant Addiction: A Neural Systems Perspective (2002, positive): “Although it was originally imagined that such plasticity occurred between glutamate terminals originating in PFC and midbrain DA neurons, anatomical studies have shown that PFC afferents to the VTA synapse on mesoaccumbens GABA, rather than DA, neurons (Carr and Sesack, 2000).”
Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “Injection of fluorescent retrobeads into different brain areas of adult mice and subsequent anatomical analysis of coronal brain slices demonstrated that DA neurons in medial posterior VTA (PN and medial PBP) selectively project to the NAc medial shell and core, medial prefrontal cortex (PFC), and b”