Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing
- Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing
- Sisi Ma; Anthony P. Pawlak; 조제원; David H. Root; David J. Barker; Mark O. West
- Dorsolateral striatum; Amphetamine; Motoric behavior
- Issue Date
- Behavioural brain research
- VOL 244, 152-161
- Amphetamine elicits motoric changes by increasing the activity of central neurotransmitters such as
dopamine and serotonin, but how these neurochemical signals are transduced into motor commands is
unclear. The dorsolateral striatum (DLS), a component of the cortico-subcortical reentrant motor loop,
contains abundant neurotransmitter transporters that amphetamine could affect. It has been hypothesized
that DLS medium spiny neurons contribute to amphetamine’s motor effects. To study striatal activity
contributing to amphetamine-induced movements, activity of DLS neurons related to vertical head movement
was recorded while tracking head movements before and after acute amphetamine injection.
Relative to saline, all amphetamine doses induced head movements above pre-injection levels, revealing
an inverted U-shaped dose–response function. Lower doses (1 mg/kg and 2 mg/kg, intraperitoneal)
induced a greater number of long (distance and duration) movements than the high dose (4 mg/kg),
which induced stereotypy. Firing rates (FR) of individual head movement neurons were compared before
and after injection during similar head movements, defined by direction, distance, duration, and apex.
Changes in FR induced by amphetamine were co-determined by dose and pre-injection FR of the neuron.
Specifically, all doses increased the FRs of slower firing neurons but decreased the FRs of faster firing
neurons. The magnitudes of elevation or reduction were greater at lower doses, but less pronounced at
the high dose, forming an inverted U function. Modulation of DLS firing may interfere with sensorimotor
processing. Furthermore, pervasive elevation of slow firing neurons’ FRs may feed-forward and increase
excitability in thalamocortical premotor areas, contributing to the increased movement initiation rate.
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