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:

• Kim J, Kondratyev A, Gale K.  Antiepileptic Drug-Induced Neuronal Cell Death in the Immature Brain: Effects of Carbamazepine, Topiramate, and Levetiracetam as Monotherapy versus Polytherapy.
  J Pharmacol Exp Ther.  323(1):165-73. 2007
• Katz I, Kim J, Gale K, Kondratyev A. Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. J Pharmacol Exp Ther.  322(2):494-500. 2007
• Wellman LL, Gale K, Malkova L.GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques. J Neurosci. 25:4577-86, 2005
• Fornai F, Busceti CL, Kondratyev A, Gale K:  AMPA receptor desensitization as a determinant of vulnerability to focally evoked status epilepticus.  Eur J Neurosci. 21:455-63, 2005
• Kondratyev A, Gale K:  Latency to onset of status epilepticus determines molecular mechanisms of seizure-induced cell death.
  Brain Res Mol Brain Res. 121:86-94, 2004
• Richardson KA, Gluckman BJ, Weinstein SL, Glosch CE, Moon JB, Gwinn RP, Gale K, Schiff SJ. In Vivo Modulation of Hippocampal Epileptiform Activity with Radial Electric Fields. Epilepsia 44:768-777, 2003
• Kondratyev A, Ved R, Gale K. The effects of repeated minimal electroconvulsive shock exposure on levels of mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic regions. Neuroscience 114:411-416, 2003
• Kondratyev A, Ved R, Gale K. The effects of repeated minimal electroconvulsive shock exposure on levels of mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic regions. Neuroscience  114:411-416, 2002
• Gwinn RP, Kondratyev A, Gale K. Time-dependent increase in basic fibroblast growth factor protein in limbic regions following electroshock seizures.  Neuroscience 114:403-409, 2002
• Kondratyev A, Selby D, Gale K. Status epilepticus leads to the degradation of the endogenous inhibitor of caspase-activated DNase in rats. Neurosci Lett 319:145-148, 2002
• Kondratyev A, Gale K. Temporal and spatial patterns of DNA fragmentation following focally or systemically-evoked status epilepticus in rats. Neurosci Lett. 310:13-16, 2001
• Dybdal D, Gale K. Postural and anticonvulsant effects of inhibition of the rat subthalamic nucleus. J Neurosci. 20:6728-33, 2000
• Kondratyev A, Gale K.  Intracerebral injection of caspase-3 inhibitor prevents neuronal apoptosis after kainic acid-evoked status epilepticus. Brain Res Mol Brain Res. 75:216-24, 2000

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