An assessment of the contributions of the pedunculopontine tegmental and cuneiform nuclei to anxiety and neophobia

Abstract

The pedunculopontine tegmental and cuneiform nuclei are adjacent structures in the mesopontine tegmentum. The pedunculopontine has attracted interest because of its extensive reciprocal connections with corticostriatal systems and possible role in complex behavioral and cognitive processes; the cuneiform is thought to be part of a neural system important for organizing defensive behaviors. Excitotoxic lesions of the pedunculopontine have been shown to affect a variety of complex functions, including learning and attention, but it has been suggested that a consequence of lesions here is the production of an anxiety-like state. We present experiments to clarify the relative role of the pedunculopontine and cuneiform nuclei in anxiety-like states in rats, measured using the elevated plus maze, food neophobia and palatability tests, and by open field behavior. In addition, we measured (through Fos expression) the effect that being on the elevated plus maze had on the pedunculopontine and cuneiform nuclei. Bilateral ibotenate lesions of cuneiform increased anxiety-like responses on the elevated plus maze, food neophobia and open field tests. Bilateral ibotenate lesions of pedunculopontine that spared cuneiform did not produce anxiety-like behavior, but did disinhibit performance in all the tests. Lesions directed at the pedunculopontine produced anxiety-like effects only when there was also significant damage in the cuneiform. The data are discussed in terms of the relationships these nuclei have with different neural systems: pedunculopontine can be understood in terms of its hierarchical relationships with forebrain systems, while cuneiform is understood best in terms of its role in regulating responses to threatening stimuli.