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. 2015 Oct 23:9:394.
doi: 10.3389/fnins.2015.00394. eCollection 2015.

Circuits regulating pleasure and happiness: the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates

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Circuits regulating pleasure and happiness: the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates

Anton J M Loonen et al. Front Neurosci. .

Abstract

The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory, and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and relate to more sophisticated behavioral manifestations such as mood. An animal comparable to lampreys was the earliest known vertebrate with a modern forebrain consisting of old and new cortical parts. Lampreys have a separate dorsal pallium, the forerunner of the most recently developed part of the cerebral cortex. In addition, the lamprey extrapyramidal system (EPS), which regulates movement, is modern. However, in lampreys and their putative forerunners, the hagfishes, the striatum, which is the input part of this EPS, probably corresponds to the human centromedial amygdala, which in higher vertebrates is part of a system mediating fear and anxiety. Both animals have well-developed nuclear habenulae, which are involved in several critical behaviors; in lampreys this system regulates the reward system that reinforces appetitive-seeking behavior or the avoidance system that reinforces flight behavior resulting from negative inputs. Lampreys also have a distinct glutamatergic nucleus, the so-called habenula-projection globus pallidus, which receives input from glutamatergic and GABAergic signals and gives output to the lateral habenula. Via this route, this nucleus influences midbrain monoaminergic nuclei and regulates the food acquisition system. These various structures involved in motor regulation in the lampreys may be conserved in humans and include two complementary mechanisms for reward reinforcement and avoidance behaviors. The first system is associated with experiencing pleasure and the second with happiness. The activities of these mechanisms are regulated by a tract running via the habenula to the upper brainstem. Identifying the human correlate of the lamprey habenula-projecting globus pallidus may help in elucidating the mechanism of the antidepressant effects of glutamatergic drugs.

Keywords: addiction; amygdala; depression; evolution of CNS; habenula; ketamine; striatum.

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Figures

Figure 1
Figure 1
Schematic representation of the nervous system of the planarian flatworm. © A. J. M. Loonen.
Figure 2
Figure 2
Simplified representation of the extrapyramidal system of lampreys (left) and humans (right) (Stephenson-Jones et al., , ; Loonen and Ivanova, 2013). In lampreys, the internal and external parts of the globus pallidus are intermingled within the dorsal pallidum but functionally segregated. GPe, globus pallidus externa; GPi, globus pallidus interna; NTP, nucleus tuberculi posterior; PPN, pedunculopontine nucleus; SNr, substantia nigra pars reticulata; STh, subthalamic nucleus. Left figure: red, glutamatergic; blue, GABAergic; green, dopaminergic; orange, cholinergic. Right figure: red, excitatory; blue, inhibitory. © A. J. M. Loonen.
Figure 3
Figure 3
Human brain with striatum (blue), nuclear amygdala (orange), cortical amygdala (red), and hippocampus (red). © A. J. M. Loonen.
Figure 4
Figure 4
Simplified representation of the amygdaloid complex of anurans (left) and rats (right) (Pitkänen, ; Moreno and González, ; right figure reproduced with permission of author). CE, central amygdala; L, lateral amygdala; M, medial amygdala. © A. J. M. Loonen.
Figure 5
Figure 5
Schematic representation of connectivity of the hippocampal complex. © A. J. M. Loonen.
Figure 6
Figure 6
Simplified representation of the cortico-striatal processing unit in which cortical information leading to a movement is processed via an intra-cortical and (parallel) extra-pyramidal route (Loonen and Ivanova, 2013). The converging organization of the extrapyramidal circuits results in a re-entry circuit. (A) Sensory input, (B) projections to brain stem and spinal cord, and (C) projection to and from ipsilateral and contralateral cortical areas. NS, non-specific part; S, specific part. © A. J. M. Loonen.
Figure 7
Figure 7
Schematic representation of the cortical input to both parts of the nucleus accumbens in rats (Dalley et al., 2008). © A. J. M. Loonen.

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