Kinetic diversity of dopamine transmission in the dorsal striatum
Dopamine (DA), a highly significant neurotransmitter in the mammalian
central nervous system, operates on multiple time scales to affect a
diverse array of physiological functions. The significance of DA in
human health is heightened by its role in a variety of pathologies.
Voltammetric measurements of electrically evoked DA release have
brought to light the existence of a patchwork of DA kinetic domains in
the dorsal striatum (DS) of the rat. Thus, it becomes necessary to
consider how these domains might be related to specific aspects of DA's
functions. Responses evoked in the fast and slow domains are distinct
in both amplitude and temporal profile. Herein, we report that
responses evoked in fast domains can be further classified into four
distinct types, types 1–4. The DS, therefore, exhibits a total of at
least five distinct evoked responses (four fast types and one slow
type). All five response types conform to kinetic models based entirely
on first-order rate expressions, which indicates that the heterogeneity
among the response types arises from kinetic diversity within the DS
terminal field. We report also that functionally distinct subregions of
the DS express DA kinetic diversity in a selective manner. Thus, this
study documents five response types, provides a thorough kinetic
explanation for each of them, and confirms their differential
association with functionally distinct subregions of this key DA
terminal field.
The dorsal striatum is composed of five significantly different
dopamine domains. Responses
from each of these five domains exhibit significantly different
ascending and descending kinetic profiles and return to a long lasting
elevated dopamine state, termed the dopamine hang-up. All features of
these responses are modeled with high correlation using first-order
modeling as well as our recently published restricted diffusion model
of evoked dopamine overflow. We also report that functionally distinct
subregions of the dorsal striatum express selective dopamine kinetic
diversity.
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Figure 1:
The five dorsal striatum (DS) responses (Type 1 in blue, Type 2 in red,
Type 3 in green, Type 4 in purple, Slow in orange). The solid lines are
the averages of the responses and the dotted lines are the SEMs: the n
values are listed on the figure. The black bar below the curves denotes
the duration of medial forebrain bundle (MFB) stimulation (black square
indicates the onset of stimulation and the black triangles mark the end
of the stimulus).
Figure 2:
Striatal mapping along Track a (top) and Track b (bottom). Right
Panels: the boxes show the anatomical location of each recording site
and the number of fast responses observed at each location (red
represents fast and blue represents slow). Left Panels: average of the
responses long Track a and Track b (n = 10 electrodes per track, 1
track each per rat; SEMS reported in Figure S5).
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