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α 2 Adrenergic Modulation of Hippocampal CA3 Network Activity
Author(s) -
Jurgens Chris W.D.,
King Jacob,
Boese Sarah,
Lichter Jessica,
Nelson Brian,
Davis Kylie,
Porter James,
Doze Van
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a253-a
Subject(s) - hippocampal formation , rauwolscine , epileptogenesis , hippocampus , chemistry , agonist , neuroscience , antagonist , epilepsy , medicine , norepinephrine transporter , endocrinology , receptor , biology , yohimbine , serotonin
Norepinephrine (NE) has been shown to have profound effects on epileptogenesis. The CA3 region of the hippocampus is believed to be a common focus in temporal lobe epilepsy, generating a type of epileptiform activity which propagates throughout the brain. Our previous work suggests that NE attenuates CA3 burst discharge activity by activating an α 2 adrenergic receptor (AR) expressed on hippocampal CA3 pyramidal cells. To characterize the α 2 AR responsible for decreasing hippocampal epileptiform activity; a pharmacological profile for various α 2 AR agonists was generated. EC 50 values obtained were consistent with an α 2 AR‐mediated response. To confirm the involvement of α 2 ARs, Schild regressions were constructed from concentration‐response curves using the AR agonist epinephrine in the presence of the selective α 2 AR antagonist RS79948. The pA 2 values obtained correlated with affinity values for α 2 ARs. Similar experiments were performed in the presence of subtype‐selective α 2 AR antagonists. pA 2 values obtained from rauwolscine, BRL44408 and ARC 239, correlated with affinities for the α 2A AR. Surgical and pharmacological isolation of CA3 pyramidal neurons suggest that NE is acting locally on these cells. These results suggest that NE is directly inhibiting hippocampal CA3 burst activity through the α 2A AR. Insight into this effect may lead to a greater understanding of how NE modulates hippocampal networks and its role in epilepsy. This study was funded by NSF CAREER Award 0347259 (VAD), ND EPSCoR through NSF EPS‐0447679 (VAD) and NIH 5P20RR017699 from the COBRE program (JEP, VAD).