title: Impaired hippocampal LTP in inbred mouse strains can be rescued by beta-adrenergic receptor activation.
abstract: Long-term potentiation (LTP), an activity-dependent enhancement of synaptic strength, and memory can be influenced by neuromodulatory transmitters such as norepinephrine (NE) and also by genetic background. beta-Adrenergic receptor activation can facilitate the expression of hippocampal CA1 LTP induced by weak stimulus patterns, but its influence on LTP induced by stronger stimulus patterns is unclear. We examined neural NE and dopamine (DA) levels, beta-adrenergic receptor expression and hippocampal LTP in genetically diverse inbred mouse strains. Brain tissue levels of NE were significantly lower in strains 129S1/SvImJ (129), BALB/cByJ (BALB) and C3H/HeJ (C3H) than in C57BL/6NCrlBR (B6). Western blot analysis showed that hippocampal beta(1)-adrenergic receptor expression was similar in strains B6, 129 and C3H, but was increased in BALB. LTP was induced in area CA1 of hippocampal slices by four trains of high-frequency stimulation (HFS) of the Schaeffer collaterals in the four inbred strains. Two hours after induction, LTP was significantly reduced in strains 129, BALB and C3H compared to B6, correlating with neural NE levels. We rescued hippocampal LTP in strains 129, BALB and C3H to levels seen in B6 by bath application of 1 microm isoproterenol, a beta-adrenergic receptor agonist, during HFS. Propranolol, a beta-adrenergic receptor antagonist, blocked this rescue in 129, BALB and C3H but did not affect LTP in strain B6. Thus, although this form of multitrain LTP does not rely on beta-adrenergic receptor activation, our data show that pharmacological activation of beta-adrenergic receptors during multiple trains of HFS can rescue CA1 LTP in genetically diverse strains with impaired LTP.
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. lesleyschimanski@hotmail.com
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Schimanski
authors.forename: Declan W
authors.initials: DW
authors.lastname: Ali
authors.forename: Glen B
authors.initials: GB
authors.lastname: Baker
authors.forename: Peter V
authors.initials: PV
authors.lastname: Nguyen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000293:injuries / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000235:genetics / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D004298:Dopamine; D009638:Norepinephrine