Dopamine-glutamate neuron projections to the nucleus accumbens medial shell and behavioral switching

doi:10.1016/j.neuint.2019.104482

Neurochemistry International

Volume 129, October 2019, 104482

https://doi.org/10.1016/j.neuint.2019.104482 Get rights and content

Highlights

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Dopamine-glutamate neurons project selectively to the Nucleus accumbens Shell.
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In the NAc medial Shell, the dopamine-glutamate neurons drive cholinergic interneurons to fire in bursts.
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Dopamine-glutamate neurons are involved in behavioral switching.
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The neurons appear to gate a switch task mode.

Abstract

Dopamine (DA) neuron projections to the striatum are functionally heterogeneous with diverse behavioral roles. We focus here on DA neuron projections to the nucleus accumbens (NAc) medial Shell, their distinct anatomical and functional connections, and discuss their role in motivated behavior. We first review rodent studies showing that a subpopulation of DA neurons in the medial ventral tegmental area (VTA) project to the NAc medial Shell. Using a combinatorial strategy, we show that the majority of DA neurons projecting to the NAc Shell express vesicular glutamate transporter 2 (VGLUT2) making them capable of glutamate co-transmission (DA-GLU neurons). In the NAc dorsal medial Shell, all of the DA neuron terminals arise from DA-GLU neurons, while in the lateral NAc Shell, DA neuron terminals arise from both DA-GLU neurons and DA-only neurons, without VGLUT2. DA-GLU neurons make excitatory connections to the three major cells types, spiny projection neurons, fast-spiking interneuron and cholinergic interneurons (ChIs). The strongest DA-GLU neuron excitatory connections are to ChIs. Photostimulation of DA-GLU neuron terminals in the slice drives ChIs to burst fire. Finally, we review studies that address specially the behavioral function of this subpopulation of DA neurons in extinction learning and latent inhibition. Taking into account findings from anatomical and functional connectome studies, we propose that DA-GLU neuron connections to ChIs in the medial Shell play a crucial role in switching behavioral responses under circumstances of altered cue-reinforcer contingencies.

Introduction

Dopamine (DA) neurons in the ventral midbrain are distributed within the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Since the first description of these neurons (Ungerstedt, 1971), studies on SNc DA neurons have focused on motor behavior, as loss of SNc DA neurons underpins Parkinson's disease, while studies on the function of VTA DA neurons have been associated with translation of motivation to action (Mogenson et al., 1980). VTA DA neurons projecting to limbic and cortical areas are known to regulate adaptive responses to both positive and negative reinforcers (Salamone and Correa, 2012; Zahm, 2000). In the past two decades, it has become clear that VTA DA neurons are anatomically and functionally heterogeneous and regulate different aspects of motivated behavior (Bromberg-Martin et al., 2010; Chuhma et al., 2017; Lammel et al., 2014; Morales and Margolis, 2017; Sanchez-Catalan et al., 2014; Salamone and Correa, 2012; Volman et al., 2013). This review focuses on the subpopulation of DA neurons projecting to the nucleus accumbens (NAc) medial Shell and their putative behavioral roles.

Section snippets

The medial shell of the nucleus accumbens

The majority of VTA DA neurons project to the NAc (Breton et al., 2019; Ikemoto, 2007; Swanson, 1982), which is further divided into three subregions, the medial Shell, lateral Shell and the Core (Groenewegen et al., 1991; Voorn et al., 2004). The NAc medial Shell is distinguished from other NAc subregions by dense afferents from the infralimbic prefrontal cortex, the anterior paraventricular thalamus, the ventral hippocampus, parvocellular basal lateral amygdala, dorsolateral septum, lateral

DA-GLU neurons preferentially project to the NAc medial Shell

In the rodent, DA neurons comprise between 50 and 60% of VTA neurons (Breton et al., 2019; Nair-Roberts et al., 2008; Yetnikoff et al., 2014) and are dispersed within several subregions, including the parabrachial pigmented nucleus (PBP), paranigral nucleus (PN), caudal linear nucleus (CLi), interfascicular nucleus (IF) and rostral linear nucleus of the raphe (RLi) (Fig. 1A). The dense VTA projections to the NAc subregions are largely ipsilateral and follow a medial-lateral topography (Fig. 1B)

Effects of DA neuron glutamate cotransmission in the NAc Shell

Selective photostimulation of DA neuron terminals in different brain regions using optogenetics enabled comprehensive mapping of DA neuron connections, revealing the remarkable complexity of the ventral midbrain DA neuron signals and their regional heterogeneity (Chuhma et al., 2014; Kabanova et al., 2015; Mingote et al., 2015; Pérez-López et al., 2018; Straub et al., 2014; Stuber et al., 2010; Tritsch et al., 2012; Tecuapetla et al., 2010; Wieland et al., 2014). Several new modes of DA neuron

Salient events activate DA neurons projecting to the NAc Shell

DA neurons modulate motivation through their actions in the NAc (Floresco, 2015; Salamone and Correa, 2012). Burst firing of DA neurons is often observed during aversive, appetitive or novel events, and during the presentation of cues in the environment predicting positive or negative reinforcement (Bromberg-Martin et al., 2010; Hamid et al., 2016; Saddoris et al., 2015). In the NAc Shell, activity of DA neurons reflects salience of events and instigates responses directed towards salient

DA neurons projecting to the NAc medial Shell signal changes in contingencies and promote behavioral switching

DA neuron control of motivated behavior involves the capacity to facilitate switching between behaviors (Eveden and Robbins, 1983; Oades, 1985; Weiner and Feldon, 1997; Redgrave et al., 1999). Changes in DA transmission in the NAc Shell modulate the degree to which competing behavioral repertoires interfere with ongoing behavior. For example, DA receptor antagonism in the medial Shell does not block food consumption (Baldo et al., 2002; Berridge and Robinson, 1998; Nowend et al., 2001; Salamone

How DA neuron GLU cotransmission in the NAc medial Shell might facilitate behavioral switching

Studies examining behavioral effects of lesions or inactivation of the NAc Shell suggest that a major role of the NAc Shell is to suppress competing behaviors that interfere with ongoing goal-directed responses (Floresco, 2015). Thus, in fully predicted circumstances, activation of SPNs in the NAc Shell promotes a Stay on task mode by inhibiting projection areas and blocking competing behavior patterns (Fig. 7A). However, in ambiguous circumstances, inhibition of SPNs promotes a Switch task

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Dopamine-glutamate neuron projections to the nucleus accumbens medial shell and behavioral switching

Highlights

Abstract

Introduction

Section snippets

The medial shell of the nucleus accumbens

DA-GLU neurons preferentially project to the NAc medial Shell

Effects of DA neuron glutamate cotransmission in the NAc Shell

Salient events activate DA neurons projecting to the NAc Shell

DA neurons projecting to the NAc medial Shell signal changes in contingencies and promote behavioral switching

How DA neuron GLU cotransmission in the NAc medial Shell might facilitate behavioral switching

Neuron

Behav. Brain Res.

Cell

Brain Res. Rev.

Neuron

Neuroscience

Cell Rep.

Neuron

Biol. Psychiatry

Brain Res.

Behav. Brain Res.

Neuroscience

Neuroscience

Brain Res. Rev.

Neuroscience

Neuroscience

Neuron

Neuropharmacology

Neuron

Neuron

Prog. Neurobiol.

Brain Res. Rev.

Neuroscience

Neuroscience

Pharmacol. Biochem. Behav.

Neuron

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Neuron

Neuroscience

Neuroscience

Neuron

Neuroscience

Neuroscience

Neuroscience

Brain Res. Bull.

Aversive stimuli differentially modulate real-time dopamine transmission dynamics within the nucleus accumbens core and shell

J. Neurosci.

Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding

Psychopharmacology

Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum

J. Neurosci.

Modulation of feeding-induced activation of mesolimbic dopamine transmission by appetitive stimuli and its relation to motivational state: limbic dopamine and feeding

Eur. J. Neurosci.

Changes in dopamine transmission in the nucleus accumbens shell and core during ethanol and sucrose self-administration

Front. Behav. Neurosci.

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat

J. Comp. Neurol.

Relative contributions and mapping of ventral tegmental area dopamine and GABA neurons by projection target in the rat

J. Comp. Neurol.

The patterns of afferent innervation of the core and shell in the “accumbens” part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold

J. Comp. Neurol.

Dopamine cells differentially regulate striatal cholinergic transmission across regions through corelease of dopamine and glutamate

Cell Rep.

Dopamine neuron glutamate cotransmission evokes a delayed excitation in lateral dorsal striatal cholinergic interneurons

eLife

Neuron-type-specific signals for reward and punishment in the ventral tegmental area

Nature

Thalamic regulation of sucrose seeking during unexpected reward omission

Neuron

GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons

Nat. Neurosci.