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Karen Gale Professor of Pharmacology |
Laboratory research projects focus on specific neural networks in the brain and their role in neurological disorders. Currently, special attention is devoted to the limbic system and the basal ganglia, with respect to glutamate and GABA-mediated influences on epileptic seizures and memory. Also under investigation are neural substrates of Parkinsonism and cocaine-induced hyperkinesias.
My co-workers and I have identified the substantia nigra as a critical site of action of GABA agonists and glutamate antagonists for protecting against experimental seizures. We have discovered a crucial site in the prepiriform cortex (named area tempestas) of the rat and monkey, from which complex partial epileptic seizures can be triggered. Our current research is aimed at determining how GABA, glutamate, serotonin, and norepinephrine interact in these brain regions to influence forebrain excitability.
In experiments, drugs are applied into discrete regions of the brain of awake animals to selectively manipulate local synaptic transmission. Acute behavioral and EEG seizure activity are evaluated, as well as short and long term molecular changes (e.g., in the expression of genes encoding neurotrophic factors) in response to seizure activity.
Related projects under development include: a) patch clamp recordings of area tempestas neurons in brain slices; b) the use of viral vectors to manipulate the genetic expression of enzymes involved in the synthesis of certain neurotransmitters in specific brain regions in vivo in an attempt to reduce seizure susceptibility; c) positron emission tomography (PET) studies of changes in regional brain metabolism during seizures; and d) determining the role of glutamate transmission in piriform cortex for recognition memory.
Selected Publications:
DesJardin JT, Holmes AL, Forcelli PA, Cole CE, Gale JT, Wellman LL, Gale K, Malkova L:
Defense-like behaviors evoked by pharmacological disinhibition of the superior colliculus in the primate.
J Neurosci 33:150-155, 2013
Dybdal D, Forcelli PA, Dubach M, Oppedisano M, Holmes A, Malkova L, Gale K:
Topography of dyskinesias and torticollis evoked by inhibition of substantia nigra pars reticulata.
Mov Disord Oct 31 epub, 2012
Holmes AL, Forcelli PA, Desjardin JT, Decker AL, Teferra M, West EA, Malkova L, Gale K:
Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata.
J Neurosci 32:13326, 2012
West EA, Forcelli PA, Murnen AT, McCue DL, Gale K, Malkova L.
Transient inactivation of basolateral amygdala during selective satiation disrupts reinforcer devaluation in rats.
Behav Neurosci 126:562, 2012
Forcelli PA, Kozlowski R, Snyder C,
Kondratyev A, Gale K.
Effects of neonatal antiepileptic drug exposure on
cognitive, emotional, and motor function in adult rats.
J Pharmacol Exp Ther 340:558, 2012
Forcelli PA, Kim J, Kondratyev A, Gale K.
Pattern of antiepileptic drug-induced cell death in limbic
regions of the neonatal rat brain.
Epilepsia 52:e207, 2011
West EA,
Desjardin JT, Gale K, Malkova L.
Transient inactivation of orbitofrontal cortex blocks
reinforcer devaluation in macaques.
J Neurosci 31:15128-35, 2011 Crowe SL,
Tsukerman S, Gale K, Jorgensen TJ, Kondratyev AD.
Phosphorylation of histone H2A.X as an early marker of
neuronal endangerment following seizures in the adult rat
brain. J Neurosci.
31(21):7648-56, 2011
Forcelli PA, Gale K, Kondratyev
A.
Early postnatal exposure of rats to
lamotrigine, but not phenytoin, reduces seizure threshold in
adulthood. Epilepsia. 52:E20-2, 2011.
Malkova L, Kozikowski AP, Gale K.
The effects of huperzine A and IDRA 21 on visual recognition
memory in young macaques. Neuropharmacology60:1262, 2011
West EA, Forcelli PA, Murnen A, Gale K, Malkova L.
A visual, position-independent instrumental reinforcer
devaluation task for rats. J Neurosci Methods194:297, 2011
Besio WG, Gale KN, Medvedev AV.
Possible therapeutic effects of transcutaneous electrical
stimulation via concentric ring electrodes.
Epilepsia. 51:85-7,
2010
Forcelli
PA, Janssen MJ, Stamps LA, Sweeney C, Vicini S, Gale K.
Therapeutic strategies to avoid long-term adverse outcomes
of neonatal antiepileptic drug exposure.
Epilepsia.
51:18-23,
2010
Kim J,
Gale K, Kondratyev A.
Effects of repeated minimal electroshock seizures on NGF,
BDNF and FGF-2 protein in the rat brain during postnatal
development. Int J Dev Neurosci.
28:227-32, 2010 Conti G, Gale K, Kondratyev A:
Immunohistochemical evaluation of the protein expression of
nerve growth factor and its TrkA receptor in rat limbic
regions following electroshock seizures.
Neurosci Res. 2009.
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