Excitatory regulation of central dopaminergic neurones

• Main Author: Lokwan, S. J. A.
• Published: Swansea University 1999
• Subjects: 612.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637946

The regulation of midbrain dopaminergic (DAergic) neurones by excitatory afferents, especially afferents which utilise excitatory amino acids (EAAs), was investigated using single unit extracellular recording and iontophoretic techniques in chloral hydrate anaesthetised rats. It is well documented that DAergic neurones fire action potentials in a pattern which consists of single spikes or bursts. Evidence suggests that tonically active EAAergic afferents induce burst firing in DAergic neurones. Since the pedunculopontine tegmental nucleus (PPTg) is one source of EAAergic afferents, its potential role in mediating burst firing in DAergic neurones was investigated. Single pulse electrical stimulation applied to the PPTg (and other sites in the rostral pons) elicited a response in the majority of DAergic neurones located in the substantia nigra pars compacta (A9 cell group), consisting of long-latency, long-duration excitations (E responses) or inhibition-excitations (IE responses). 37% of responses elicited by stimulation of the PPTg contained bursts closely time-locked to the stimulation: non-PPTg sites were less effective in this regard. The bursts themselves had a mean latency of 96.2 ms, which is shorter than that of bursts in A9 DAergic neurones elicited by stimulation of the medial prefrontal cortex (mPFC; 152 ms). Since the mPFC has been implicated in the production of bursts in DAergic neurones, the present results raise the possibility that bursts arise in these cells via a polysynaptic route which involves the PPTg. It has recently been hypothesised that bursts in DAergic neurones are initiated by a burst of activity in EAAergic afferent fibres. This burst activates receptors of the N-methyl-D-aspartate subtype of EAA receptor to produce a slow depolarising wave in the cell.