title: Gating of hippocampal output by β-adrenergic receptor activation in the pilocarpine model of epilepsy.
abstract: Norepinephrine acting via β-adrenergic receptors (β-ARs) plays an important role in hippocampal plasticity including the subiculum which is the principal target of CA1 pyramidal cells and which controls information transfer from the hippocampus to other brain regions including the neighboring presubiculum and the entorhinal cortex (EC). Subicular pyramidal cells are classified as regular- (RS) and burst-spiking (BS) cells. Activation of β-ARs at CA1-subiculum synapses induces long-term potentiation (LTP) in burst- but not in RS cells (Wójtowicz et al., 2010). To elucidate seizure-associated disturbances in the norepinephrine-dependent modulation of hippocampal output, we investigated the functional consequences of the β-AR-dependent synaptic plasticity at CA1-subiculum synapses for the transfer of hippocampal output to the parahippocampal region in the pilocarpine model of temporal lobe epilepsy. Using single-cell and multi-channel field recordings in slices, we studied β-AR-mediated changes in the functional connectivity between CA1, the subiculum and its target-structures. We confirm that application of the β-adrenergic agonist isoproterenol induces LTP in subicular BS- but not RS cells. Due to the distinct spatial distribution of RS- and BS cells in the proximo-to-distal axis of the subiculum, in field recordings, LTP was significantly stronger in the distal than in the proximal subiculum. In pilocarpine-treated animals, β-AR-mediated LTP was strongly reduced in the distal subiculum. The attenuated LTP was associated with a disturbed polysynaptic transmission from the CA1, via the subiculum to the presubiculum, but with a preserved transmission to the medial EC. Our findings suggest that synaptic plasticity may influence target-related information flow and that such regulation is disturbed in pilocarpine-treated epileptic rats.
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Grosser
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: J-O
authors.initials: JO
authors.lastname: Hollnagel
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: K E
authors.initials: KE
authors.lastname: Gilling
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Bartsch
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Heinemann
authors.affiliation: Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany; Department of Psychiatry and Psychotherapy, Medical School Brandenburg - Campus Neuruppin, Neuruppin, Germany. Electronic address: joachim.behr@charite.de.
authors.forename: J
authors.initials: J
authors.lastname: Behr
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation; D008297:Male; D020534:Parahippocampal Gyrus / Q000187:drug effects / Q000503:physiopathology; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D010862:Pilocarpine; D007545:Isoproterenol
keywords: isoproterenol; multi-electrode array; seizures; subiculum; temporal lobe epilepsy