• Johnson, Steven (PI)

Project: Research project

Project Details


The ultimate goal of this research is to investigate mechanisms of action
of dopamine and acetylcholine in the neostriatum. This research may have
important clinical ramifications since dysfunction of these
neurotransmitter systems is implicated in the pathophysiology of
Parkinson's disease, Huntington's chorea and tardive dyskinesia. Previous
electrophysiologic studies used voltage recording which cannot directly
measure neuronal conductance. Also, most past studies recorded from
unidentified neuronal type. Recent studies show that the mammalian
striatum consists of a neuronal patch and matrix system, identified by a
range of immunohistochemical markers. Retrograde labelling studies also
show that patch and matrix neurons have different afferent and efferent
connections. We propose to use single electrode voltage clamp to record
ionic currents and characterize receptor-mediated responses on identified
patch and matrix neurons. Brain slices will be used in vitro. Intrinsic
membrane properties will be studied, and intrastriatal as well as cortical
stimulation will be used to evoked synaptic activity. Drugs (receptor
agonists and antagonists) will be added to the superfusing solution and
their effects measured at steady-state concentrations. Schild plots will
be constructed and dissociation constants will be estimated. Lucifer
yellow will be injected intracellularly from the micropipette using
iontophoresis. Slices will be subsequently fixed and immunohistochemically
stained for calcium binding protein to identify the matrix. Neurons filled
with Lucifer yellow will be identified and their presence in stained matrix
or unstained patch will be noted. In further experiments, striatonigral
projection neurons will be identified by prior injection of rhodamine-
labelled microspheres into the zona compacta of the substantia nigra.
Back-filled neurons will be identified by rhodamine fluorescence at the
time of intracellular recording. Using these techniques we will
investigate receptor-mediated effects of dopamine and acetylcholine and
test the hypothesis that these neurotransmitters have opposite effects on
conductances in identified striatal neurons. We will also study post-
synaptic current generated by dopamine released synaptically in response to
intrastriatal stimulation. Pre-synaptic effects of dopamine on
neurotransmission in the corticostriatal pathway will also be studied.
Effective start/end date8/1/907/31/95


  • National Institutes of Health: $53,892.00
  • National Institutes of Health: $9,113.00


  • Medicine(all)
  • Neuroscience(all)


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