Contemporary approaches to neural circuit manipulation and mapping: focus on reward and addiction

Abstract

One contribution of 15 to a theme issue 'Controlling brain activity to alter perception, behaviour and society'. Tying complex psychological processes to precisely defined neural circuits is a major goal of systems and behavioural neuroscience. This is critical for understanding adaptive behaviour, and also how neural systems are altered in states of psychopathology, such as addiction. Efforts to relate psychological processes relevant to addiction to activity within defined neural circuits have been complicated by neural heterogeneity. Recent advances in technology allow for manipulation and mapping of genetically and anatomically defined neurons, which when used in concert with sophisticated behavioural models, have the potential to provide great insight into neural circuit bases of behaviour. Here we discuss contemporary approaches for understanding reward and addiction, with a focus on midbrain dopamine and cortico-striato-pallidal circuits.

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

“…As detailed above, the multiplexed neurotransmission of the VTA-VGluT2 neurons is an emerging factor involved in the complexity of VTA function. Based on observations that different combinations of neurotransmitters are multiplexed throughout the brain (Trudeau 2004; Gillespie et al 2005; Zhou et al, 2005; Gras et al, 2008; Noh et al, 2010; Higley et al, 2011; Tritsch et al 2012; Hnasko and Edwards, 2012 Münster-Wandowski et al, 2013; Nelson et al, 2014; Root et al, 2014a; Shabel et al, 2014; Qi et al, 2014; Zhang et al, 2015; Fattorini et al, 2015; Saunders et al, 2015), we suggest that multiplexed neurotransmission conveys distinct messages depending on the neurotransmitter content of each circuit, momentary singular or multiplexed signaling, and perhaps even the time scale of neurotransmitter function. Furthermore, we speculate that changes in the influence of one or more of the multiplexed neurotransmitters, by way of either presynaptic of postsynaptic changes, may result from and result in observable changes in behavior.…”

“…In addition, there is evidence for GABA and DA co-transmission in by substantia nigra pars compacta neurons as well as retinal amacrine neurons (Tritsch et al 2012; Hirasawa et al, 2012). Other forms of neurotransmission include GABA and histamine by hypothalamic neurons (Yu et al, 2015), glutamate and acetylcholine co-transmission in striatal interneurons or medial habenula neurons (Gras et al, 2008; Ren et al, 2011; Higley et al, 2011; Nelson et al, 2014), GABA and acetylcholine co-transmission in corticopetal globus pallidus neurons (Saunders et al, 2015). …”

“…In the present review, we cover recent literature on the diversity of VTA neuronal phenotypes as they relate to ‘multiplexed neurotransmission’. We refer the reader to recent comprehensive reviews detailing VTA cellular composition, VTA efferent and afferents, and VTA functions(Oades & Halliday, 1987; Fields et al, 2007; Ikemoto, 2007; Nair-Roberts et al, 2008; Morales & Pickel, 2012; Trudeau et al, 2014; Morales & Root 2014; Pignatelli and Bonci, 2015; Saunders et al, 2015; Luthi and Luscher, 2014). Moreover, the present review does not cover co-transmission of neurotransmitters and neuropeptides, which has long been known and recently reviewed (Morales & Pickel, 2012).…”

Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior

“…Most commonly, studies have utilized methodology that involves optogenetic inhibition at the virus infusion site (to target discrete brain nuclei) or at the terminal region of the target circuit following virus injection at the cell body region, even though these approaches are more prone to affect fibers of passage (Beyeler et al, 2016;Stamatakis and Stuber, 2012). In particular, the combinatorial viral approach is essential (a) to manipulate proteins that are not expressed at the terminal region of target circuits and (b) to mitigate the current scarcity of Cre-driver lines and unavailability of Cre-dependent opsins packaged in retrogradely transported viruses (Saunders et al, 2015;Witten et al, 2011;Warden et al, 2014). One caveat is that retrograde transport efficiency in various AAV serotypes appears to vary across species (Aschauer et al, 2013;Rothermel et al, 2013).…”

Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking

“…The relevant neural circuitry is incompletely understood from the brainwide to cellular level, but studies of reward and aversion circuitry have identified separate and overlapping networks (Haber and Knutson, 2010). Reward circuitry is heavily dependent upon ventral tegmental area (VTA) dopamine neurons and their targets, which include cortex and nucleus accumbens (NAc) as well as additional corticostriatal circuitry involving the ventral pallidum, anterior cingulate cortex and medial prefrontal cortex (mPFC), and diverse other structures spanning amygdala, hippocampus, thalamus, and habenular and brainstem nuclei (Robbins and Everitt, 1996; Saunders et al, 2015). Processing of aversion (Hayes and Northoff, 2011) can involve many of these same structures as well (Lammel et al, 2011; Lammel et al, 2012; Tan et al, 2012), but with a distinct involvement of lateral habenula, bed nucleus of the stria terminalis, hypothalamus, and periaqueductal gray matter.…”