Orbitomedial prefrontal cortical projections to hypothalamus in the rat.

A previous study in the rat revealed that distinct orbital and medial prefrontal cortical (OMPFC) areas projected to specific columns of the midbrain periaqueductal gray region (PAG). This study used anterograde tracing techniques to define projections to the hypothalamus arising from the same OMPFC regions. In addition, injections of anterograde and retrograde tracers were made into different PAG columns to examine connections between hypothalamic regions and PAG columns projected upon by the same OMPFC regions. The most extensive patterns of hypothalamic termination were seen after injection of anterograde tracer in prelimbic and infralimbic (PL/IL) and the ventral and medial orbital (VO/MO) cortices. Projections from rostral PL/IL and VO/MO targeted the rostrocaudal extent of the lateral hypothalamus, as well as lateral perifornical, and dorsal and posterior hypothalamic areas. Projections arising from caudal PL/IL terminated within the dorsal hypothalamus, including the dorsomedial nucleus and dorsal and posterior hypothalamic areas. There were also projections to medial perifornical and lateral hypothalamic areas. In contrast, it was found that anterior cingulate (AC), dorsolateral orbital (DLO), and agranular insular (AId) cortices projected to distinct and restricted hypothalamic regions. Projections arising from AC terminated within dorsal and posterior hypothalamic areas, whereas DLO and AId projected to the lateral hypothalamus. The same OMPFC regions also projected indirectly, by means of specific PAG columns, to many of the same hypothalamic fields. In the context of our previous findings, these data indicate that, in both rat and macaque, parallel but distinct circuits interconnect OMPFC areas with specific hypothalamic regions, as well as PAG columns.

Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat.

We utilised retrograde and anterograde tracing procedures to study the origin and termination of prefrontal cortical (PFC) projections to the periaqueductal gray (PAG) in the rat. A previous study, in the primate, had demonstrated that distinct subgroups of PFC areas project to specific PAG columns. Retrograde tracing experiments revealed that projections to dorsolateral (dlPAG) and ventrolateral (vlPAG) periaqueductal gray columns arose from medial PFC, specifically prelimbic, infralimbic, and anterior cingulate cortices. Injections made in the vlPAG also labeled cells in medial, ventral, and dorsolateral orbital cortex and dorsal and posterior agranular insular cortex. Other orbital and insular regions, including lateral and ventrolateral orbital, ventral agranular insular, and dysgranular and granular insular cortex did not give rise to appreciable projections to the PAG. Anterograde tracing experiments revealed that the projections to different PAG columns arose from specific PFC areas. Projections from the caudodorsal medial PFC (caudal prelimbic and anterior cingulate cortices) terminated predominantly in dlPAG, whereas projections from the rostroventral medial PFC (rostral prelimbic cortex) innervated predominantly the vlPAG. As well, consistent with the retrograde data, projections arising from select orbital and agranular insular cortical areas terminated selectively in the vlPAG. The results indicate: (1) that rat orbital and medial PFC possesses an organisation broadly similar to that of the primate; and (2) that subdivisions within the rat orbital and medial PFC can be recognised on the basis of projections to distinct PAG columns.

Cardiovascular effects of microinjections of opioid agonists into the 'Depressor Region' of the ventrolateral periaqueductal gray region.

Microinjections of excitatory amino acids made into the ventrolateral midbrain periaqueductal gray of the rat have revealed that neurons in this region integrate a reaction characterised by quiescence, hyporeactivity, hypotension and bradycardia. Microinjections of both excitatory amino acids and opioids into the ventrolateral periaqueductal gray have shown also that it is a key central site mediating analgesia. The effects of injections of opioids into the ventrolateral periaqueductal gray on arterial pressure and heart rate or behaviour are unknown. In this study we first mapped in the rat the extent of the ventrolateral periaqueductal gray hypotensive region as revealed by microinjections of excitatory amino acids. We found that ventrolateral periaqueductal gray depressor region extended more rostrally than previously thought into the tegmentum ventrolateral to the periaqueductal gray. Subsequently we studied for the first time, the effects of microinjections of mu-, delta-, and kappa-opioid agonists made into the ventrolateral periaqueductal grey depressor region. In contrast to the effects of excitatory amino acid injections, microinjections of the mu-opioid agonist ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) evoked hypertension and tachycardia at approximately 50% of sites. Similar to excitatory amino acid injections, microinjections of both the delta-opioid agonist ([D-Pen2,D-Pen5]enkephalin), and the kappa-opioid agonist ((5,7,8)-(+)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-y l]-benzeneacetamide) evoked either a hypotension and bradycardia, or had no effect. These results indicate that different opiate receptor subtypes are present on a distinct population of ventrolateral periaqueductal gray neurons, or at different ventrolateral periaqueductal gray synaptic locations (pre- or post-synaptic).

Projections from the ventrolateral periaqueductal gray to endocrine regulatory subdivisions of the paraventricular nucleus of the hypothalamus in the rat.

The ventrolateral periaqueductal gray (vlPAG) mediates quiescence, hyporeactivity, hypotension and bradycardia, a pattern of response evoked by injury or social defeat. These stimuli also evoke increased levels of vasopressin (VP) and adrenocorticotrophic hormone (ACTH). A key central nervous system (CNS) locus mediating endocrine changes is the paraventricular nucleus of the hypothalamus (PVH). We investigated the extent of vlPAG projections to PVH. Anterograde tracer injections into the vlPAG, revealed 'terminal' label in: (1) the medial, dorsal, anterior and lateral parvicellular divisions, and (2) lateral and medial posterior magnocellular divisions of the PVH. Deposits of the retrograde tracer Fast Blue, verified the projection to the PVH arising from the vlPAG.

A calbindin immunoreactive "deep pain' recipient thalamic nucleus in the rat.

The ventrolateral periaqueductal gray (vlPAG) is the only brain region known to receive convergent deep noxious inputs and to mediate the reactions characteristic of deep pain. Injections of biotinylated dextran into the vlPAG of the rat revealed a strong projection to a discrete, calbindin terminal-immunoreactive region of the caudal ventromedial nucleus (VMc) of the thalamus. This nucleus appears homologous to the calbindin-positive, pain- and temperature-specific-posterior ventromedial thalamic region of primates. We suggest that the vlPAG to VMc projection represents an important new route via which deep noxious inputs reach thalamus. As the rat is the species of choice in most experimental studies of pain, the functional-anatomical definition of this projection should further investigation of the thalamic representation of deep pain.