Local connections between the columns of the periaqueductal gray matter: a case for intrinsic neuromodulation

Abstract

Chemical stimulation of the midbrain periaqueductal gray matter (PAG) in conscious animals produces opposite responses (viz., defensive behavior and pressor responses from the lateral PAG column vs. quiescence and depressor responses from the ventrolateral PAG column), raising the possibility that PAG columns are interconnected. To test this hypothesis, two types of anatomical experiments were performed in rats. First, the anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) was injected into individual PAG columns or adjoining regions which included the Edinger–Westphal, dorsal raphe, and precommissural nuclei. Ten days later, the intrinsic PAG projections were studied. Our results show that each PAG column projects bilaterally to all of the other PAG columns, and also provides local connections within its own column. Furthermore, the Edinger–Westphal and precommissural nuclei project to all four PAG columns, while the dorsal raphe nucleus projects only to the ventrolateral and lateral columns. In a second experiment, we found that cardiovascular-related PAG projection neurons of both the lateral and ventrolateral columns receive inputs from the reciprocal PAG column. This was demonstrated by a double tracer neuroanatomical study in which PHA-L was first iontophoretically ejected into either the lateral or ventrolateral PAG columns and then, several days later the retrograde transneuronal viral tracer, pseudorabies virus, was injected into the stellate sympathetic ganglion. Intra-PAG circuits were visualized by a dual immunohistochemical procedure. These results suggest that during the fight-or-flight response when the `fight' program is activated, the `flight' PAG network may be inhibited and the converse situation may occur during the flight response.