NEUROPLASTICITY IN DAMAGED CATECHOLAMINERGIC SYSTEMS

  • Abercrombie, Elizabeth (PI)
  • Bohnen, Nicholas (PI)
  • Schallert, Timothy (PI)
  • Woodward, Donald (PI)
  • Zigmond, Michael (PI)
  • Sved, Alan (PI)
  • Hastings, Teresa (PI)
  • Sesack, Susan (PI)
  • Lewis, David (PI)
  • Abercrombie, Elizabeth (PI)
  • Zigmond, Michael (PI)
  • Hastings, Teresa (PI)
  • Sesack, Susan (PI)
  • Lewis, David (PI)
  • Sved, Alan (PI)
  • WOODWARD, DONALD JAY (PI)
  • Schallert, Timothy (PI)

Project Details

Description

Evidence from clinical observations and experimental investigations
indicates that few enduring functional impairments are produced by subtotal
damage to monoaminergic neurons, despite considerable evidence for their
involvement in a wide variety of physiological and behavioral processes.
We have proposed that this apparent paradox results from the capacity for
"synaptic homeostasis" that exists in these systems and that leads to
compensatory events occurring after partial injury. We propose to use a
multidisciplinary approach to describe at the cellular level the initial
deficits, recovery of function and residual deficits produced by subtotal
destruction of such a monoaminergic system and then to explore the
biological bases of those phenomena. Our work will focus on the
dopaminergic projection of the nigrostriatal bundle. Where appropriate,
other monoaminergic systems will be used for these studies, including the
sympathoadrenal system and the noradrenergic locus coeruleus-hippocampus
projection. First, we will examine the impact of subtotal injury on
monoaminergic function as determined by biochemical, physiological,
electrophysilogical, and behavioral measurements. Second, we will attempt
to determine the biological bases of the sparing of function that occurs
after moderate lesions and the recovery of function that occurs after
larger lesions. Third, we will test the ability of certain treatments to
extend recovery of striatal function. Fourth, we will examine several
other states which may be related to lesion induced-hypoinnervation,
including development and chronic neuroleptic treatment. Finally, we will
examine the influence of the age at which brain injury is sustained on the
behavioral and biological consequences. These results should provide
insights into the neurobiology of monoaminergic systems under normal
conditions and after damage, as well as provide information of relevance to
the detection and treatment of subclinical brain damage in disorders
involving abnormalities of monoamine-containing systems.
StatusFinished
Effective start/end date12/31/898/31/10

ASJC

  • Medicine(all)
  • Neuroscience(all)
  • Clinical Neurology
  • Neurology
  • Biochemistry
  • Physiology
  • Surgery
  • Pathology and Forensic Medicine
  • Immunology