NeuropharmacologyGlutamate synaptic inputs to ventral tegmental area neurons in the rat derive primarily from subcortical sources
Section snippets
Subjects and surgeries
As approved by the Institutional Animal Care and Use Committee at the University of Pittsburgh and in accordance with the NIH Guide for the Care and Use of Laboratory Animals, tract-tracing experiments were performed on six adult male Sprague–Dawley rats (Hilltop Laboratory Animals Inc., Scottsdale, PA, USA, 330–360 g). Three additional naive rats were used to determine the optimal dilution of antibodies directed against VGlut1 or VGlut2 and to examine single labeling for these proteins within
Light microscopy
The injections of the retrograde tracer FG into the NAc and PFC were conducted in a manner similar to those used in our previous studies (Carr and Sesack 2000, Omelchenko and Sesack 2005, Omelchenko and Sesack 2006a) and produced comparable results. Visualized by immunoperoxidase, FG filled both the core and shell subdivisions of the NAc at mid rostro-caudal levels (Fig. 1A), whereas FG injections into the PFC were placed within prelimbic and infralimbic areas (terminology according to Krettek
Discussion
This study represents the first ultrastructural comparison of VTA inputs from glutamate axons expressing VGlut1 versus VGlut2 as putative markers of cortical versus subcortical origins, respectively. The larger size, higher density, more frequent convergence, and more proximal contacts observed for VGlut2+ axons suggest that subcortical glutamate inputs to the VTA predominate over cortical sources of excitation in driving behaviorally-linked burst firing in DA cells. Other morphological
Acknowledgments
Support was provided by USPHS grant NIMH 067937. The authors gratefully acknowledge the technical contributions of Maureen Walsh, the statistical consulting assistance of Dr. Allan Sampson at the University of Pittsburgh, and the generous supply of antibodies provided by Dr. Robert Edwards at the University of California at San Francisco.
References (89)
- et al.
Molecular and functional analysis of a novel neuronal vesicular glutamate transporter
J Biol Chem
(2001) - et al.
GABA-labeled terminals form proportionally more synapses with dopaminergic neurons containing low densities of tyrosine hydroxylase-immunoreactivity in rat ventral tegmental area
Brain Res
(1991) - et al.
Neurokinin B and substance P genes are co-expressed in a subset of neurons in the rat habenula
Neuropeptides
(1989) - et al.
Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata
Brain Res
(2001) - et al.
An excitatory amino acid projection from rat prefrontal cortex to periaqueductal gray
Brain Res Bull
(1986) - et al.
Glutamate-like immunoreactivity in neurons of the laterodorsal tegmental and pedunculopontine nuclei in the rat
Neurosci Lett
(1990) - et al.
Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area
Neuroscience
(2002) - et al.
VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate
Trends Neurosci
(2004) - et al.
The expression of vesicular glutamate transporters defines two classes of excitatory synapse
Neuron
(2001) - et al.
Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain
Neuroscience
(2004)
Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain
Brain Res Mol Brain Res
Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) in the cerebellum and precerebellar nuclei of the rat
Brain Res Mol Brain Res
Complementary distribution of vesicular glutamate transporters in the central nervous system
Neurosci Res
Quantal analysis and synaptic anatomy-integrating two views of hippocampal plasticity
Trends Neurosci
Stimulation of the pedunculopontine tegmental nucleus in the rat produces burst firing in A9 dopaminergic neurons
Neuroscience
A comparison of the effects of electrical stimulation of the lateral and ventromedial hypothalamus on the activity of neurons in the ventral tegmental area and substantia nigra
Brain Res Bull
The cortico-nigral projection in the rat: an anterograde tracing study with biotinylated dextran amine
Brain Res
An ultrastructural size principle
Neuroscience
Is the short-latency dopamine response too short to signal reward error?
Trends Neurosci
Pedunculopontine-evoked excitation of substantia nigra neurons in the rat
Brain Res
Reward prediction in primate basal ganglia and frontal cortex
Neuropharmacology
GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain
Brain Res
Numerous GABAergic afferents to locus ceruleus in the pericerulear dendritic zone: possible interneuronal pool
J Neurosci
Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex
Cereb Cortex
The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission
J Neurosci
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Brain Res Brain Res Rev
Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey
Science
Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities
J Cell Biol
Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons
J Neurosci
Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry
J Comp Neurol
Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo
Eur J Neurosci
Glutamate-like immunoreactivity is present within cholinergic neurons of the laterodorsal tegmental and pedunculopontine nuclei
Adv Exp Med Biol
Phasic activation of substantia nigra and the ventral tegmental area by chemical stimulation of the superior colliculus: an electrophysiological investigation in the rat
Eur J Neurosci
Two populations of glutamatergic axons in the rat dorsal raphe nucleus defined by the vesicular glutamate transporters 1 and 2
Eur J Neurosci
Dopamine neurons in culture express VGLUT2 explaining their capacity to release glutamate at synapses in addition to dopamine
J Neurochem
Frequent coexpression of the vesicular glutamate transporter 1 and 2 genes, as well as coexpression with genes for choline acetyltransferase or glutamic acid decarboxylase in neurons of rat brain
J Neurosci Res
How visual stimuli activate dopaminergic neurons at short latency
Science
Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area
Eur J Neurosci
Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection
Neuropsychopharmacology
The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate
Proc Natl Acad Sci U S A
Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites
Science
Changes of immunocytochemical localization of vesicular glutamate transporters in the rat visual system after the retinofugal denervation
J Comp Neurol
Glutamatergic afferents of the ventral tegmental area in rat
Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions
J Comp Neurol
Cited by (96)
Inquiry of the orbitofrontal cortex role in incentive learning: An artificial neural networks simulation
2023, Cognitive Systems ResearchCharacterisation of methylphenidate-induced excitation in midbrain dopamine neurons, an electrophysiological study in the rat brain
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryNicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats
2022, NeuropharmacologyCitation Excerpt :Moreover, acute and chronic nicotine-induced anxiety-like behavior is reversed by LHb lesion (Casarrubea et al., 2015). Both morphological and functional evidence demonstrated the existence of an indirect inhibitory control exerted by the LHb over VTA DA neuronal activity via the rostro-medial tegmental nucleus (RMTg) (Christoph et al., 1986; Lammel et al., 2012; Lecca et al., 2011; Lecca et al., 2012; Omelchenko and Sesack, 2007). However, there are no functional data in vivo illustrating how LHb neuronal activity is affected by acute and chronic nicotine exposure.
Synaptically located nicotinic acetylcholine receptor subunits in neurons involved in dependency to nicotine
2019, Neuroscience of Nicotine: Mechanisms and TreatmentRole of glutamatergic system and mesocorticolimbic circuits in alcohol dependence
2018, Progress in Neurobiology