Pedunculopontine arousal system physiology-Effects of psychostimulant abuse

Abstract

This review describes the interactions between the pedunculopontine nucleus (PPN), the ventral tegmental area (VTA), and the thalamocortical system. Experiments using modulators of cholinergic receptors in the PPN clarified its role on psychostimulant-induced locomotion. PPN activation was found to be involved in the animal's voluntary search for psychostimulants. Every PPN neuron is known to generate gamma band oscillations. Voltage-gated calcium channels are key elements in the generation and maintenance of gamma band activity of PPN neurons. Calcium channels are also key elements mediating psychostimulant-induced alterations in the thalamic targets of PPN output. Thus, the PPN is a key substrate for maintaining arousal and REM sleep, but also in modulating psychostimulant self-administration.

Keywords: Amphetamine; Cocaine; Dopamine; Nicotine; P/Q-type calcium channels; T-type calcium channels.

Fig. 1

Schematic diagram showing psychostimulants/neuromodulators of PPN and thalamocortical circuits. Projections from PPN to key dopaminergic nuclei underlying psychostimulant effects. The PPN projects to the ventral tegmental area (VTA) and substantia nigra (SN). Dopaminergic VTA neurons in turn project to the medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). Amphetamines/cocaine (two stimulants that exert their effects by drastically increasing extracellular DA concentration) self-administration can be modulated by PPN efferents to VTA and SN. Cholinergic modulation by the PPN can modulate VTA and thalamic nuclei, exciting glutamatergic relay neurons while inhibiting GABAergic reticular thalamic neurons. Upper left box: (+) represents excitatory, glutamatergic or cholinergic synapses, and (−) GABAergic, or cholinergic inhibitory synapses.

Fig. 2

Illustration of psychostimulant/neuromodulator dependent turnover of calcium and cationic hyperpolarization-activated I_H currents on PPN and thalamocortical neurons. Systemic administration of cocaine is known to up-regulate membrane expression of T-type calcium and I_H cationic currents , , . Systemic administration of METH reduced P/Q type calcium channel currents in medial prefrontal cortex (mPFC) . In addition, nicotine upregulated I_H cationic current density in PPN neurons (Garcia-Rill et al. [80]).