Circuits Regulating Pleasure and Happiness: The Evolution of the Amygdalar-Hippocampal-Habenular Connectivity in Vertebrates

Abstract

Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although, the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum) connected with the bed nucleus of the stria terminalis (pallidum). This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homolog of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a framework for the regulation of the stress response, including the medial habenula and the subgenual cingulate cortex, in which dysfunction may explain the major symptoms of mood and anxiety disorders.

The roles of the orbitofrontal cortex via the habenula in non-reward and depression, and in the responses of serotonin and dopamine neurons

“…The medial habenula receives septal inputs, and projects to the interpeduncular nucleus and 5-HT neurons (see Fig. 1) (Loonen and Ivanova, 2016b;Proulx et al, 2014). Now in these considerations of the habenula, there is little that is described about from where the habenula receives its non-reward and punishment-related signals.…”

“…This provides a route for reward, non-reward, and reward prediction error signals of largely cortical origin to influence the dopamine neurons. Details of some of these anatomical connections are provided elsewhere (Loonen and Ivanova, 2016b;Proulx et al, 2014).…”

“…The medial habenula also receives septal inputs, and projects to the interpeduncular nucleus, and thereby to 5-HT neurons (and probably dopamine neurons) (see Fig. 1) (Loonen and Ivanova, 2016b;Proulx et al, 2014).…”

Circuits regulating pleasure and happiness: evolution and role in mental disorders

“…We have hypothesised that the same may be true in humans (6,7). Within the extrapyramidal circuits, the human homologue of GPh may be localised within the border region of the globus pallidus (GPb) (17) and the ventral pallidum (51).…”

Consider Role of Glutamatergic Habenula-projecting Globus Pallidus in OCD

“…We have recently studied the evolution of the brain structures regulating distress-avoiding and reward-seeking behaviours [2,3]. Since these behaviours are essential to maintain life, they should have been regulated by the brains of all our human vertebrate ancestors [4].…”