Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex of the rat

Abstract

Increasing evidence shows that the rostral agranular insular cortex (RAIC) is important in the modulation of nociception in humans and rats and that dopamine and GABA appear to be key neurotransmitters in the function of this cortical region. Here we use immunocytochemistry and path tracing to examine the relationship between dopamine and GABA related elements in the RAIC of the rat. We found that the RAIC has a high density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra (VTA/SN) and from a different set of neurons than those that project to the medial prefrontal cortex. Within the RAIC, there are close appositions between dopamine fibers and GABAergic interneurons. One target of cortical GABA appears to be a dense band of GABAB receptor-bearing neurons located in lamina 5 of the RAIC. The GABAB receptor-bearing neurons project principally to the amygdala and nucleus accumbens with few or no projections to the medial prefrontal cortex, cingulate gyrus, the mediodorsal thalamic nucleus or contralateral RAIC. The current anatomical data, together with previous behavioral results, suggest that part of the dopaminergic modulation of the RAIC occurs through GABAergic interneurons. GABA is able to exert specific effects through its action on GABAB receptor-bearing projection neurons that target a few subcortical limbic structures. Through these connections, dopamine innervation of the RAIC is likely to affect the motivational and affective dimensions of pain.

Insular hypocretin transmission regulates nicotine reward

“…It is therefore likely that hypocretin transmission in other brain regions may also contribute to this process. For example, the shell region of the nucleus accumbens, a brain area critically involved in the reinforcing effects of addictive drugs, receives afferent input from the agranular and dysgranular regions of the insular cortex (29). Further, the agranular insula receives innervation from reward-relevant brain regions including the ventral tegmental area (29), amygdala, and prefrontal cortex (30).…”

“…For example, the shell region of the nucleus accumbens, a brain area critically involved in the reinforcing effects of addictive drugs, receives afferent input from the agranular and dysgranular regions of the insular cortex (29). Further, the agranular insula receives innervation from reward-relevant brain regions including the ventral tegmental area (29), amygdala, and prefrontal cortex (30). Thus, it is an interesting possibility that hypocretin transmission in other portions of the insula, particularly the agranular insula, or in other reward-relevant brain regions such as the ventral tegmental area (10,31), may also regulate the motivational properties of nicotine.…”

Cerebral cortex modulation of pain

“…The effect of dopamine is mediated by different receptors; ie, the activation of D (2) and the blockade of D(1) receptors elicit antinociception, since the dopamine D(1) receptor antagonist SCH-23390 and dopamine D(2) receptor agonist TNPA caused decreases in the autotomy score and a delay in the onset in the neuropathic pain model induced by denervation [54] . The RAIC has a higher density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra and from a set of neurons different from those that project to the medial prefrontal cortex [13] . Additionally, there are close appositions between dopamine fibers and GABAergic interneurons within the RAIC [13] .…”

“…The RAIC has a higher density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra and from a set of neurons different from those that project to the medial prefrontal cortex [13] . Additionally, there are close appositions between dopamine fibers and GABAergic interneurons within the RAIC [13] . These data suggest that part of the dopaminergic modulation of the RAIC may occur through GABAergic interneurons.…”

“…These cortical structures constitute, respectively, the medial and lateral pain systems, the nucleus submedius (Sm)-VLO-periaqueductal gray (PAG) system and the motor cortex system [3][4][5][7][8][9][10][11] . Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine transmitters, are involved in the modulation of pain by these cortical structures [11][12][13][14][15] . This paper reviews recent studies on pain modulation by the aforementioned cerebral cortex structures in animals and human.…”