Neural Circuit Mechanism Underlying the Feeding Controlled by Insula-Central Amygdala Pathway

Dissecting a disynaptic central amygdala-parasubthalamic nucleus neural circuit that mediates cholecystokinin-induced eating suppression

“…Because CEA PKC-δ+ neurons suppress eating by inhibiting CEA PKC-δ− neurons [ [41] , [42] , [43] , [44] ], neurons downstream of CEA PKC-δ− neurons involved in eating suppression should be disinhibited (i.e., “activated”) by the activation of CEA PKC-δ+ neurons ( Figure 1 A). However, CEA PKC-δ+ neurons are also involved in non-CCK-mediated eating suppression such as bitter taste [ 41 ], suggesting some neurons activated by the CEA PKC-δ+ neuron activation may not be involved in CCK's effect.…”

“…Although CEA neurons are activated by CCK or refeeding after fasting [ 13 , 36 , 37 ], a general CEA lesion yields small or no effect on food intake [ 38 , 39 ]. This lack of effect is likely due to the cellular complexity of CEA [ 35 , 40 ], in which different types of neurons with disparate or even opposing functions in eating are intermingled and complicated circuit structure is involved [ [41] , [42] , [43] , [44] ]. Due to these complexities, the brain region downstream of the CEA that regulates CCK-induced eating suppression remains unknown.…”

“…Importantly, a thorough survey of CEA neurons labeled by distinct genetic markers revealed that the PKC-δ+ neurons in the lateral part of CEA are the only population in the CEA that is preferentially activated by CCK [ 42 ]. It has also been demonstrated that CEA PKC-δ+ neurons suppress eating by inhibiting local GABAergic PKC-δ negative neurons (CEA PKC-δ− ) [ [41] , [42] , [43] , [44] ]. The genetic identification of the CEA PKC-δ+ neurons thus provides a unique tool to determine the neurons downstream of the CEA that mediate the eating-suppressing effect of CCK.…”

Volume and Connectivity Differences in Brain Networks Associated with Cognitive Constructs of Binge Eating

“…BN subjects showed reduced connectivity between the central nucleus of the amygdala (CeA) and the hypothalamus in the right hemisphere, and the ventral anterior insula in the left hemisphere (Frank et al, 2016). Connectivity between the CeA and insula has been associated with feeding behaviour in rats (Zhang-Molina et al, 2020), with activation of this pathway suppressing food intake. Projections of the CeA and insula also converge in the parasubthalamic nucleus, which together with the CeA and insula modulate feeding behaviour of palatable food (Barbier et al, 2020).…”

Brain Signaling of Indispensable Amino Acid Deficiency

“…The central nucleus of the amygdala (CEA) contains at least 3 distinct populations of neurons, each of which inhibits the others. Increased feeding is associated with cells containing the serotonin 2A receptors, whereas decreased feeding neurons contain the kinase, PKC-delta; both are found in neurons that are considered late firing cells [ 69 ]. In addition, the insular cortex has been implicated in CTA after a few hours.…”