Karen N. Gale, PhD
Professor of Pharmacology
University of Washington, 1975
Dr. Gale’s laboratory is interested neural networks in the limbic system and basal ganglia as substrates for the regulation of complex behavior and cognitive function in intact animals. Her studies have direct relevance to several neuropsychiatric disorders including schizophrenia, Korsakoff’s syndrome, ParkinsonÕs disease, AlzheimerÕs, HuntingtonÕs disease, epilepsy and manic-depressive illness. Her research on basal ganglia aims to understand how interactions between dopaminergic, GABAergic and glutamatergic pathways regulate posture, attention, movement and excitability in rodents and primates. Dr. Gale’s research on limbic system networks aims to understand the neurochemical and neuroanatomical substrates for both memory and seizure generation in both rats and nonhuman primates. These studies utilize focal drug application and viral vector gene transfection into discrete brain areas in an effort to reveal the functional role of specific neurotransmitter pathways. She has recently discovered that the piriform-prefrontal-perirhinal-thalamic circuitry important for epileptogenesis is also a critical network for visual recognition memory. Moreover, while the hippocampus is not required for either seizure generation or memory, it is able to dynamically modulate both processes; the nature of this modulation in rats and monkeys is being explored in Dr. Gale’s laboratory.
Another area of research focus in Dr. Gale’s laboratory concerns the neuroprotective and plasticity-promoting effect of repeated, brief noninjurious seizures. This research effort seeks to understand the changes in gene expression associated with exposure to electroconvulsive shock. Expression of genes encoding trophic factors, transcription factors, death-promoting and survival-promoting factors are being examined to identify essential contrasts between injurious and protective seizure events. These studies, which utilize in situ hybridization, PCR, RNase protection and Western blotting, are expected to contribute to our understanding of how controlled seizures may be therapeutic (as in the treatment of bipolar psychiatric disorders, and potentially, for neurodegenerative disorders) and how the set point for programmed cell death in neurons is dynamically regulated by synaptic activity.
- 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 R, 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 1;20(17):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 22;75(2):216-24, 2000