Assistant Professor in Pharmacology
Georgetown University, 2011
Current Research: 1. Vulnerability of the developing brain to drug induced damage - Anti-seizure medications (also called anticonvulsant or antiepileptic drugs) are the mainstay of treatment for epilepsy. However, the use of these medications in special populations (e.g., pregnant women with epilepsy, neonates with seizures) poses a challenge due to the exquisite sensitivity of the developing brain to perturbations of neural activity. Many commonly utilized anti seizure drugs induce apoptosis in the neonatal rat brain, disrupt functional and morphological synaptic development, and alter behavioral function. We are continuing to examine this class of drugs to characterize effects on brain development, identify mechanisms of toxicity and search for therapeutic approaches to minimize long-term effects. We employ a combination of histological, biochemical, physiological, behavioral and imaging approaches to address these questions.
2. Hippocampal and basal ganglia circuits in seizure progression. The same neural circuits through which seizures propagate are vital participants in normal cognitive and emotional function. We are examining hippocampal and basal ganglia contributions to both normal behavior and to seizure propagation. To determine the role of these circuits we are using a combination of lesions, focal pharmacological (in rodents and primates), electrical, and state of the art pharmacogenetic and optogenetic methods. These techniques are used to perturb circuit function during behavioral tasks as well as in animal models of seizures/epilepsy. Finally, we are also assessing the ability of shRNA-mediated knockdown of select targets within these circuits to delay or prevent the development of epilepsy.
- Aguilar BL, Forcelli PA, Malkova L: Inhibition of the substantia nigra pars reticulata produces divergent effects on sensorimotor gating in rats and monkeys. Sci Rep. 8:9369, 2018.
- Wicker E, Turchi J, Malkova L, Forcelli PA: Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques. Elife. 7, 2018.
- Waguespack HF1, Málková L2, Forcelli PA3, Turchi J: Effects of systemic cholinergic antagonism on reinforcer devaluation in macaques. Neurosci Lett. 678:62-67, 2018.
- André EA, Forcelli PA, Pak DT: What goes up must come down: homeostatic synaptic plasticity strategies in neurological disease. Future Neurol. 13:13-21, 2018.
- Al-Muhtasib N, Sepulveda-Rodriguez A, Vicini S, Forcelli PA: Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons. Epilepsia. 59:333-344, 2018.
- Lee Y, Rodriguez OC, Albanese C, Santos VR, Cortes de Oliveira JA, Donatti ALF, Fernandes A, Garcia-Cairasco N, N'Gouemo P, Forcelli PA: Divergent brain changes in two audiogenic rat strains: A voxel-based morphometry and diffusion tensor imaging comparison of the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR). Neurobiol Dis. 111:80-90, 2018.
- Klein P, Dingledine R, Aronica E, Bernard C, Blümcke I, Boison D, Brodie MJ, Brooks-Kayal AR, Engel J Jr, Forcelli PA, Hirsch LJ, Kaminski RM, Klitgaard H, Kobow K, Lowenstein DH, Pearl PL, Pitkänen A, Puhakka N, Rogawski MA, Schmidt D, Sillanpää M, Sloviter RS, Steinhäuser C, Vezzani A, Walker MC, Löscher W: Commonalities in epileptogenic processes from different acute brain insults: Do they translate? Epilepsia. 59:37-66, 2018.
- Dunn R, Queenan BN, Pak DTS, Forcelli PA: Divergent effects of levetiracetam and tiagabine against spontaneous seizures in adult rats following neonatal hypoxia. Epilepsy Res. 140:1-7, 2018.
- Queenan BN, Dunn RL, Santos VR, Feng Y, Huizenga MN, Hammack RJ, Vicini S, Forcelli PA, Pak DTS: Kappa opioid receptors regulate hippocampal synaptic homeostasis and epileptogenesis. Epilepsia. 59:106-122, 2018.
- Forcelli PA: Applications of optogenetic and chemogenetic methods to seizure circuits: Where to go next?. J Neurosci Res. 95:2345-2356, 2017.
- Huizenga MN, Wicker E, Beck VC, Forcelli PA: Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats. Epilepsia. 58:1593-1602, 2017.
- Forcelli PA, Waguespack HF, Malkova L: Defensive Vocalizations and Motor Asymmetry Triggered by Disinhibition of the Periaqueductal Gray in Non-human Primates. Front Neurosci. 11:163,2017.
- Forcelli PA, Wellman LL, Malkova L: Blockade of glutamatergic transmission in the primate basolateral amygdala suppresses active behavior without altering social interaction. Behav Neurosci.;131(2):192-200,2017.
- Wellman LL, Forcelli PA, Aguilar BL, Malkova L.: Bidirectional Control of Social Behavior by Activity within Basolateral and Central Amygdala of Primates. J Neurosci.;36(33):8746-56.,2016.
- Forcelli PA, DesJardin JT, West EA, Holmes AL, Elorette C, Wellman LL, Malkova L. PA.:
- Wicker E, Forcelli PA. PA.: Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures. Exp Neurol.;404-12,2016.
- Partridge JG, Forcelli PA, Luo R, Cashdan JM, Schulkin J, Valentino RJ, Vicini S.PA.: Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis. Neuropharmacology.;107:239-50,2016.
- Brown L, Gutherz S, Kulick C, Soper C, Kondratyev A, Forcelli PA.: Profile of retigabine-induced neuronal apoptosis in the developing rat brain. Epilepsia.;57(4):660-70,2016.
- Frankel S, Medvedeva N, Gutherz S, Kulick C, Kondratyev A, Forcelli PA.: Comparison of the long-term behavioral effects of neonatal exposure to retigabine or phenobarbital in rats. Epilepsy Behav.;57(Pt A):34-40, 2016.
- Kaushal S, Tamer Z, Opoku F, Forcelli PA.: Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia. 57(5):727-34,2016.
- Forcelli PA, DesJardin JT, West EA, Holmes AL, Elorette C, Wellman LL, Malkova L.: Amygdala selectively modulates defensive responses evoked from the superior colliculus in non-human primates. Soc Cogn Affect Neurosci ahead of print,2016.
- Wellman LL, Forcelli PA, Aguilar BL, Malkova L. : Bidirectional Control of Social Behavior by Activity within Basolateral and Central Amygdala of Primates. J Neurosci. 36(33):8746-56, 2016.
- Wicker E, Forcelli PA: Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures. Epub ahead of print, 2016.
- Partridge JG, Forcelli PA, Luo R, Cashdan JM, Schulkin J, Valentino RJ, Vicini S: Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis. Neuropharmacology 107:239-50,2016
- Soper C, Wicker E, Kulick CV, N'Gouemo P, Forcelli PA: Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks. Neurobiol Dis 87:102-115, 2016.
- Forcelli PA, Turner JR, Lee BG, Olson TT, Xie T, Xiao Y, Blendy JA, Kellar KJ: Anxiolytic- and Antidepressant-like Effects of the Methadone Metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP). Neuropharmacology. 101:46-56, 2016.
- Vismer MS, Forcelli PA, Skopin MD, Gale K, Koubeissi MZ: The piriform, perirhinal, and entorhinal cortex in seizure generation.. JFront Neural Circuits. 9:27, 2015
- Malkova L, Forcelli PA, Wellman LL, Dybdal D, Dubach MF, Gale K: Blockade of glutamatergic transmission in perirhinal cortex impairs object recognition memory in macaques.. J Neurosci. 35(12):5043-50, 2015
- Forcelli PA: Short- and long-term neurological and psychiatric sequelae of developmental exposure to antiepileptic and anesthetic drugs.. Front Neurol. 6:41, 2015
- Credle JJ, Forcelli PA, Delannoy M, Oaks AW, Permaul E, Berry DL, Duka V, Wills J, Sidhu A: α-Synuclein-mediated inhibition of ATF6 processing into COPII vesicles disrupts UPR signaling in Parkinson's disease.. Neurobiol Dis. 76:112-25, 2015
- Wurzman R, Forcelli PA, Griffey CJ, Kromer LF: Repetitive grooming and sensorimotor abnormalities in an ephrin-A knockout model for Autism Spectrum Disorders.. Behav Brain Res 278:115-128, 2015
- Kulick CV, Gutherz SB, Beck VC, Medvedeva N, Soper C, Forcelli PA: Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in neonatal rats.. Eur J Pharmacol 749:63-68, 2014
- Gutherz SB, Kulick CV, Soper C, Kondratyev A, Gale K, Forcelli PA: Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats. Eplepsy Behav 37:265-9, 2014
- Avanzini G, Forcelli PA, Gale K: Are there really "epileptogenic" mechanisms or only corruptions of "normal" plasticity?. Adv Exp Med Biol. 813:95-107, 2014
- Ullrich L, Dumanis SB, Evans TM, Jeannotte AM, Leonard C, Rozzi SJ, Taylor CM, Gale K, Kanwal JS, Maguire-Zeiss KA, Wolfe BB, Forcelli PA: From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training. Med Ed Online 19:22623, 2014
- Kulick C, Gutherz S, Kondratyev A, Forcelli PA: Ontogenic profile of seizures evoked by the beta-carboline DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in rats. Eur J Pharmacol. 2014 Jun 23. pii: S0014-2999(14)00454-3
- Forcelli PA, Palchik G, Leath T, Desjardin JT, Gale K, Malkova L: Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys. Proc Natl Acad Sci U S A. 2014 Mar 3. [Epub ahead of print]
- Hussmann GP, Dedominicis KE, Turner JR, Yasuda RP, Klehm J, Forcelli PA, Xiao Y, Richardson JR, Sahibzada N, Wolfe BB, Lindstrom J, Blendy JA, Kellar KJ: Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J Neurochem. 2014. [Epub ahead of print]
- Forcelli PA, Kalikhman D, Gale K: Delayed effect of craniotomy on experimental seizures in rats. PLoS One. 8:e81401.2013.
- Forcelli PA, Soper C, Duckles A, Gale K, Kondratyev A : Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats. Epilepsy Res. 107:217-23.2013.
- Dumanis SB, Ullrich L, Washington PM, Forcelli PA : It's money! Real-world grant experience through a student-run, peer-reviewed program. CBE Life Sci Educ. 12:419-28.2013.
- Ullrich LE, Krafnick AJ, Dumanis SB, Forcelli PA : Drugs, the brain, and behavior: a graduate student-run comprehensive course in neuroscience. J Undergrad Neurosci Educ. 10:A105-12. Epub 2012.
- West EA, Forcelli PA, McCue DL, Malkova L : Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats. Behav Brain Res. 246:10-4. Epub 2013.
- 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. 33:150-5.2013.
- 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. 28:460-8. 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. 32:13326-32. 2012.