Heterogeneous dopamine populations project to specific subregions of the primate amygdala

Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Neuroscience (Impact Factor: 3.36). 11/2009; 165(4):1501-18. DOI: 10.1016/j.neuroscience.2009.11.004
Source: PubMed


Amygdala dysfunction has been reported among patients with various psychiatric disorders, and dopamine is critical to the amygdala's ability to mediate fear conditioning. Recent work indicates that the midbrain dopaminergic neurons have heterogeneous receptor and membrane channel profiles, as well as differential physiologic responses to discrete stimuli. To begin understanding how dopamine affects amygdala physiology and pathology in higher primates, we mapped the inputs from the midbrain dopaminergic neurons to various amygdala nuclei in the monkey using retrograde and anterograde tracing techniques, and single and double immunofluorescence histochemistry for tracer and tyrosine hydroxylase, a dopamine marker. Our results show that the primate amygdala as a whole receives broad input, mostly from the dorsal tier of the substantia nigra, pars compacta, and the A8-retrorubral field. Input from the A10-ventral tegmental area, while present, was less prominent. These results differ from data in the rat, where the midline A10-ventral tegmental area is a major source of dopamine to the amygdala "mesolimbic" pathway. Both the "amygdala proper" and the "extended amygdala" receive the majority of their input from the dorsal tier of the substantia nigra and A8-retrorubral field, but the extended amygdala receives additional modest input from the ventral tier. In addition, the "extended amygdala" structures have a denser input than the "amygdala proper," with the exception of the lateral core of the central nucleus, which receives no input. Our anterograde studies confirm these findings, and revealed fine, diffuse terminal fibers in the amygdala proper, but a denser network of fibers in the extended amygdala outside the lateral core of the central nucleus. These results indicate that the entire extent of the dorsal tier beyond the A10-ventral tegmental area may regulate the amygdala in primates, and subsequently serve as a source of dysfunction in primate psychopathology.

Download full-text


Available from: Julie L. Fudge, Dec 10, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is considerable evidence that dysfunction of the cortico-basal ganglia circuits may be associated with several mood and anxiety disorders. However, it is unclear whether circuit abnormalities contribute directly either to the neurobiology of these conditions or to the manifestation of symptoms. Understanding the role of these pathways in psychiatric illness has been limited by an incomplete characterization of normal function. In recent years, studies using animal models and human functional imaging have greatly expanded the literature describing normal cortico-basal ganglia circuit function. In this paper, recent key studies of circuit function using human and animal models are reviewed and integrated with findings from other studies conducted over the previous decades. The literature suggests several hypotheses of cortico-basal ganglia circuitry function in mood and anxiety disorders that warrant further exploration. Hypotheses are proposed herein based upon the cortico-basal ganglia mechanisms of: (1) feedforward and feedback control, (2) circuit integration and (3) emotional control. These are presented as models of circuit function, which may be particularly relevant to future investigations using neuroimaging and functional connectivity analyses.
    Brain Structure and Function 10/2010; 215(2):73-96. DOI:10.1007/s00429-010-0280-y · 5.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent electrophysiological studies on the primate amygdala have advanced our understanding of how individual neurons encode information relevant to emotional processes, but it remains unclear how these neurons are functionally and anatomically organized. To address this, we analyzed cross-correlograms of amygdala spike trains recorded during a task in which monkeys learned to associate novel images with rewarding and aversive outcomes. Using this task, we have recently described two populations of amygdala neurons: one that responds more strongly to images predicting reward (positive value-coding), and another that responds more strongly to images predicting an aversive stimulus (negative value-coding). Here, we report that these neural populations are organized into distinct, but anatomically intermingled, appetitive and aversive functional circuits, which are dynamically modulated as animals used the images to predict outcomes. Furthermore, we report that responses to sensory stimuli are prevalent in the lateral amygdala, and are also prevalent in the medial amygdala for sensory stimuli that are emotionally significant. The circuits identified here could potentially mediate valence-specific emotional behaviors thought to involve the amygdala.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2013; 33(2):722-33. DOI:10.1523/JNEUROSCI.2970-12.2013 · 6.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top-down signals from prefrontal cortex realize "cognitive control" in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior.
    Frontiers in Human Neuroscience 04/2013; 7:101. DOI:10.3389/fnhum.2013.00101 · 3.63 Impact Factor
Show more