Afferents of vocalization-controlling periaqueductal regions in the squirrel monkey

Abstract

In order to determine the input of vocalization-controlling regions of the midbrain periaqueductal gray (PAG), wheat germ agglutinin-horseradish peroxidase was injected in six squirrel monkeys (Saimiri sciureus) at PAG sites yielding vocalization when injected with the glutamate agonist homocysteic acid. Brains were scanned for retrogradely labeled areas common to all six animals. The results show that the vocalization-eliciting sites receive a widespread input, with the heaviest projections coming from the surrounding PAG, dorsomedial and ventromedial hypothalamus, medial preoptic region, substantia nigra pars diffusa, zona incerta and reticular formation of the mesencephalon, pons, and medulla. The heaviest cortical input reaches the PAG from the mediofrontal cortex. Moderate to weak projections come from the insula, lateral prefrontal, and premotor cortex as well as the superior and middle temporal cortex. Subcortical moderate to weak projections reach the PAG from the central and medial amygdala, nucleus of the stria terminalis, septum, nucleus accumbens, lateral preoptic region, lateral and posterior hypothalamus, globus pallidus, pretectal area, deep layers of the superior colliculus, the pericentral inferior colliculus, mesencephalic trigeminal nucleus, locus coeruleus, substantia nigra pars compacta, dorsal and ventral raphe, vestibular nuclei, spinal trigeminal nucleus, solitary tract nucleus, and nucleus gracilis. The input of the periaqueductal vocalization-eliciting regions thus is dominated by limbic, motivation-controlling afferents; input, however, also comes from sensory, motor, arousal-controlling, and cognitive brain areas.

Introduction

The midbrain periaqueductal gray (PAG) is assumed to play an essential role in the vocal expression of emotional states. Various findings suggest that it represents a crucial relay station of the limbic vocalization pathway. Localized electrical stimulation of the PAG has been shown to produce species-specific vocalization in numerous species (for review, see Ref. [45]). Vocalization can also be obtained by injection of glutamate agonists and GABA antagonists (cat: [6]; squirrel monkey: [48]), suggesting that the PAG does not only contain fibers of passage, but also synapses of the vocalization pathway. Single-unit recording studies have revealed vocalization-correlated activity in the PAG [27], [58]. Lesion studies have reported mutism after bilateral destruction of the PAG and bordering tegmentum in various experimental animals, as well as in human patients (rat: [19]; cat: [51], [83], [94]; dog: [93]; squirrel monkey: [47]; humans: [15], [30]). Partial destruction of the PAG does not affect the acoustical structure of vocalization in general, but abolishes discrete vocal reactions, while leaving others intact [47], [51], [94]. After inactivation of the PAG by injections of the GABA agonist muscimol, naturally sounding vocalization is still elicitable in regions of the caudal midbrain and rostral pons [91]. This suggests that the PAG serves gating functions rather than vocal pattern generation. In other words, its function probably is to trigger vocal output on the basis of motivational and sensory input. Neuroanatomical studies have revealed a major input from various limbic regions to the PAG [11], [16], [20], [24], [32], [38], [39], [57], [64], [66], [67], [78]. Besides limbic afferents, projections from sensory structures have been also described [8], [13], [50], [60], [65]. Apart from the Kyuhou and Gemba study [57], however, none of these studies has investigated the input into functionally verified vocalization-controlling regions of the PAG. The present study will fill this gap.