Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey

Abstract

Prefrontal cortices have been implicated in autonomic function, but their role in this activity is not well understood. Orbital and medial prefrontal cortices receive input from cortical and subcortical structures associated with emotions. Thus, the prefrontal cortex may be an essential link for autonomic responses driven by emotions. Classic studies have demonstrated the existence of projections between prefrontal cortex and the hypothalamus, a central autonomic structure, but the topographic organization of these connections in the monkey has not been clearly established. We investigated the organization of bidirectional connections between these areas in the rhesus monkey by using tracer injections in orbital, medial, and lateral prefrontal areas. All prefrontal areas investigated received projections from the hypothalamus, originating mainly in the posterior hypothalamus. Differences in the topography of hypothalamic projection neurons were related to both the location and type of the target cortical area. Injections in lateral eulaminate prefrontal areas primarily labeled neurons in the posterior hypothalamus that were equally distributed in the lateral and medial hypothalamus. In contrast, injections in orbitofrontal and medial limbic cortices labeled neurons in the anterior and tuberal regions of the hypothalamus and in the posterior region. Projection neurons targeting orbital limbic cortices were more prevalent in the lateral part of the hypothalamus, whereas those targeting medial limbic cortices were more prevalent in the medial hypothalamus. In comparison to the ascending projections, descending projections from prefrontal cortex to the hypothalamus were highly specific, originating mostly from orbital and medial prefrontal cortices. The ascending and descending connections overlapped in the hypothalamus in areas that have autonomic functions. These results suggest that specific orbitofrontal and medial prefrontal areas exert a direct influence on the hypothalamus and may be important for the autonomic responses evoked by complex emotional situations.

Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle

“…Given the role of the OFC in modulating primary regions for emotional behavior, including the amygdala and hypothalamus (21)(22)(23)(24), the results support a model of increased topdown modulation of limbic activity during the premenstrual phase. This increased activity may be primary or compensatory.…”

“…Participants consisted of 12 normal women (mean age, 28; range, [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Subjects gave informed consent before study participation (part of a Weill Medical College Institutional Review Board-approved protocol).…”

Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey

“…Patterns designating injection sites refer to the type of tracer used: black, £uorescent dyes; stripes, BDA ; black outline, [ 3 H] amino acids; gray, HRP-WGA. , 1995bDermon and Barbas, 1994;Barbas and Blatt, 1995;Rempel-Clower and Barbas, 1998), including a study restricted to description of projection neurons directed from the amygdala to the prefrontal cortex (Barbas and De Olmos, 1990). Injections of tracers included all layers of the injected cortices.…”

“…Morys et al, 1999). If con¢rmed to be excitatory through physiologic study, then medial prefrontal projections to the amygdala may amplify the output of the BLpc to the hypothalamus, a pathway that may be recruited in concert with a robust direct projection from medial prefrontal cortices to hypothalamic autonomic centers (Leichnetz and Astruc, 1976;Room et al, 1985;Rempel-Clower and Barbas, 1998;Ongur et al, 1998;Freedman et al, 2000). In addition, we noted that medial prefrontal axons terminated in the Co and Me nuclei, engaged in the expressive capacity of the amygdala in gustatory, olfactory, and reproductive functions (for review see De Olmos, 1990).…”

“…Suppression of the Ce nucleus may allow time for integration of sensory signals so that an adequate judgement can be made regarding the recruitment of autonomic sectors of the amygdala. Thus, the orbitofrontal pathway likely has a permissive e¡ect on the hypothalamus, whose activity could be further augmented by direct excitatory projections from the same orbitofrontal and medial prefrontal cortices to hypothalamic autonomic centers (Rempel-Clower and Barbas, 1998). It is envisioned that dual pathways with disinhibitory or excitatory e¡ects on the hypothalamus may be recruited when the synergistic activation of the amygdala and the orbitofrontal cortex signals an emotionally charged circumstance.…”