Abstract
Cognitive functions associated with prefrontal cortex (PFC), such as working memory and attention, are strongly influenced by catecholamine [dopamine (DA) and norepinephrine (NE)] release. Midbrain dopaminergic neurons in the ventral tegmental area and noradrenergic neurons in the locus coeruleus are major sources of DA and NE to the PFC. It is traditionally believed that DA and NE neurons are homogeneous with highly divergent axons innervating multiple terminal fields and once released, DA and NE individually or complementarily modulate the prefrontal functions and other brain regions. However, recent studies indicate that both DA and NE neurons in the mammalian brain are heterogeneous with a great degree of diversity, including their developmental lineages, molecular phenotypes, projection targets, afferent inputs, synaptic connectivity, physiological properties, and behavioral functions. These diverse characteristics could potentially endow DA and NE neurons with distinct roles in executive function, and alterations in their responses to genetic and epigenetic risk factors during development may contribute to distinct phenotypic and functional changes in disease states. In this review of recent literature, we discuss how these advances in DA and NE neurons change our thinking of catecholamine influences in cognitive functions in the brain, especially functions related to PFC. We review how the projection-target specific populations of neurons in these two systems execute their functions in both normal and abnormal conditions. Additionally, we explore what open questions remain and suggest where future research needs to move in order to provide a novel insight into the cause of neuropsychiatric disorders related to DA and NE systems.
Highlights
The prefrontal cortex (PFC) is involved in a number of cognitive and executive functions in both primates and rodents, including working memory, sustained and flexible attention (Dalley et al, 2004; Arnsten, 2009; Bari and Robbins, 2013), and is critical in guiding behavior in a complex and dynamic world
Because the locus coeruleus (LC)-NE and ventral tegmental area (VTA)-DA systems maintain reciprocal anatomical connections and appear to act synergistically and complementarily to guide behavior, advances in the study of one of these catecholamine pathways will by necessity impact study of the other
Anatomical, molecular, and physiological heterogeneity www.frontiersin.org in catecholamine nuclei may be a fundamental principle of their organization, and future studies of these structures and their efferent domains may provide a framework for better understanding acquired or genetically transmitted abnormalities of the VTA-DA and LC-NE systems that result in maladaptive behaviors including those expressed in addiction, ADHD, schizophrenia, and post-traumatic stress disorder
Summary
The prefrontal cortex (PFC) is involved in a number of cognitive and executive functions in both primates and rodents, including working memory, sustained and flexible attention (Dalley et al, 2004; Arnsten, 2009; Bari and Robbins, 2013), and is critical in guiding behavior in a complex and dynamic world. Identification of specific afferents to LC cells with specified outputs as has been shown in the DA system (Lammel et al, 2008, 2012) will further the collective understanding of the role of LC in maintaining discrete behavioral operations rather than acting as a homogeneous and uniform modulator of the activity in LC projection fields. Optogenetic approaches may provide a means of characterizing anatomic, neurochemical, and functionally specific pathways into and out of LC that maintain distinct roles and demonstrate that NE release is capable of producing unique actions in different terminal fields under diverse circumstances.
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