Translating Fear Circuitry: Amygdala Projections to Subgenual and Perigenual Anterior Cingulate in the Macaque

Abstract

Rodent fear-learning models posit that amygdala–infralimbic connections facilitate extinction while amygdala–prelimbic prefrontal connections mediate fear expression. Analogous amygdala–prefrontal circuitry between rodents and primates is not established. Using paired small volumes of neural tracers injected into the perigenual anterior cingulate cortex (pgACC; areas 24b and 32; a potential homologue to rodent prelimbic cortex) and subgenual anterior cingulate cortex (sgACC, areas 25 and 14c; a potential homologue to rodent infralimbic cortex) in a single hemisphere, we mapped amygdala projections to the pgACC and sgACC within single subjects. All injections resulted in dense retrograde labeling specifically within the intermediate division of the basal nucleus (Bi) and the magnocellular division of the accessory basal nucleus (ABmc). Areal analysis revealed a bias for connectivity with the sgACC, with the ABmc showing a greater bias than the Bi. Double fluorescence analysis revealed that sgACC and pgACC projections were intermingled within the Bi and ABmc, where a proportion were double labeled. We conclude that amygdala inputs to the ACC largely originate from the Bi and ABmc, preferentially connect to the sgACC, and that a subset collaterally project to both sgACC and pgACC. These findings advance our understanding of fear extinction and fear expression circuitry across species.

Kappa opioid receptors in the central amygdala modulate spinal nociceptive processing through an action on amygdala CRF neurons

“…In addition to coupling to brainstem centers involved in descending pain modulation, the amygdala CeA could influence spinal nociceptive processing through indirect influences on cortical regions such as ACC [ 73 , 74 ] via cholinergic neurons in substantia innominata and nucleus basalis of Meynert [ 75 ]. CeA neurons do not directly project to cortical regions; main amygdala input to ACC arises from the basolateral amygdala [ 76 ]. Therefore, the amygdala can exert facilitatory influences on spinal nociceptive processing either through ascending or descending output to pain control systems [ 73 , 77 , 78 ] by activating facilitatory or inhibiting inhibitory modulation.…”

Distribution and overlap of entorhinal, premotor, and amygdalar connections in the monkey anterior cingulate cortex

“…One important cortical route is through the ACC, which has extensive connections with entorhinal and parahippocampal cortices of the medial temporal lobe (Anderson, Bunce, & Barbas, 2016; Barbas & Blatt, 1995; Barbas & De Olmos, 1990; Blatt, Pandya, & Rosene, 2003; Blatt & Rosene, 1988; Bunce & Barbas, 2011; Insausti et al, 1987; Insausti & Amaral, 2008; Joyce & Barbas, 2018; Kondo, Saleem, & Price, 2005; Lavenex, Suzuki, & Amaral, 2002; Mohedano‐Moriano et al, 2007; Munoz & Insausti, 2005; Pandya, Van Hoesen, & Mesulam, 1981; Rempel‐Clower & Barbas, 2000; Rosene & Van Hoesen, 1977; Saleem, Kondo, & Price, 2008; Suzuki & Amaral, 2004; Zikopoulos, Hoistad, John, & Barbas, 2017), as well as, premotor cortices (Barbas & Pandya, 1987; Bates & Goldman‐Rakic, 1993; Carmichael & Price, 1995; Dum & Strick, 1992, 2002; Luppino, Rozzi, Calzavara, & Matelli, 2003; Morecraft et al, 2012). Additionally, the ACC has strong connections with the amygdala, a medial temporal structure important for regulating emotional arousal and motivational drive (Barbas & De Olmos, 1990; Barbas, Saha, Rempel‐Clower, & Ghashghaei, 2003; Ghashghaei & Barbas, 2002; Kim et al, 2018; Phelps, 2004; Sharma, Kelly, Pfeifer, & Fudge, 2019; Vogt, 2005). How these medial temporal limbic systems interact with the motor planning system, and how they converge and diverge across distinct subdivisions and cortical layers of the ACC, is not well‐understood.…”

Testing a Developmental Model of Parental Warmth, Amygdala–Subgenual Anterior Cingulate Cortex Connectivity, and Depressive Symptoms in Adolescents During the COVID-19 Pandemic

“…Another possible explanation for our findings is that the BLA, compared to other amygdala subdivisions, is involved in coordinating activity with the sgACC. Nonhuman animal research shows that amygdala projections to the ACC, including the sgACC region, originate primarily from the BLA (52,53). Adolescents in our sample had significantly stronger BLA-sgACC connectivity than CMA-sgACC connectivity.…”