Activation of presynaptic alpha7 nicotinic receptors evokes an excitatory response in hippocampal CA3 neurones in anaesthetized rats: an in vivo iontophoretic study.
OBJECTIVE
alpha7 Nicotinic receptors have been suggested to play an important role in hippocampal learning and memory. However, the direct action of this receptor subtype on hippocampal pyramidal neurones in vivo has not yet been fully investigated. The availability of selective agonists for alpha7 receptors [AR-R17779 and (R)-(-)-5'-phenylspiro[1-azabicyclo[2.2.2] octane-3,2'-(3'H)furo[2,3-b]pyridine (PSAB-OFP)] has now allowed this role to be investigated.


METHODS
Single-cell extracellular recordings were made from hippocampal CA3 pyramidal neurones in anaesthetized rats. The effects of nicotine, AR-R17779 and PSAB-OFP, applied either systemically or iontophoretically, were studied on the activity of these neurones.


RESULTS
Intravenous injection of cumulative doses of nicotine and PSAB-OFP induced dose-related, significant increases in neuronal firing in the majority of neurones tested. This excitation could be inhibited by intravenous administration of methyllycaconitine (MLA), a selective alpha7 nicotinic receptor antagonist. Furthermore, iontophoretic application of nicotine, AR-R17779 and PSAB-OFP each evoked current-dependent excitation of most CA3 pyramidal neurones studied, and this excitation was antagonized by co-iontophoretic application of MLA. In addition, the excitation induced by iontophoretic application of nicotine, AR-R17779 or PSAB-OFP was also blocked by co-iontophoretic application of either 6,7-dinitroquinoxaline-2,3-dione (DNQX) or D(2)-2-amino-5-phosphonopentanoate (D-AP5), selective N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor antagonists respectively.


CONCLUSIONS
CA3 pyramidal neurones are modulated by activation of presynaptic alpha7 nicotinic receptors, which, at least in part, enhances glutamate release onto post-synaptic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and NMDA receptors on these CA3 neurones. This mechanism probably contributes to the effects of nicotine on hippocampal learning and memory.
Huang
Lan-Ting
LT
Institutes of Brain Science and State Key Laboratory for Medical Neurobiology, Fudan University, Shanghai, China.
Sherwood
John L
JL
Sun
Ya-Jie
YJ
Lodge
David
D
Wang
Yun
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D026603:D-Aspartic Acid / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011810:Quinoxalines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds
C472510:5'-phenylspiro(1-azabicyclo(2.2.2.))octane-3,2'-(3'H)furo(2,3-b)pyridine; C408128:AR-R 17779; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D018733:Nicotinic Antagonists; D011725:Pyridines; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D013141:Spiro Compounds; C054634:methyllycaconitine; D018698:Glutamic Acid; D026603:D-Aspartic Acid; C056723:FG 9041; D016202:N-Methylaspartate; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate; C023666:pyridine; D000157:Aconitine