Fimbria-fornix lesions compromise the induction of long-term potentiation at the Schaffer collateral-CA1 synapse in the rat in vivo.
Although bilateral fimbria-fornix (FF) lesioning impairs spatial performance in animals, the literature is equivocal regarding its effects on hippocampal long-term potentiation (LTP). We examined the effects of FF lesioning on LTP induction in the Schaffer collateral-CA1 pathway in vivo with a protocol that delivered theta burst stimulation (TBS) trains of increasing length until a sufficient length was reached to induce LTP of the monosynaptic field excitatory postsynaptic potential (fEPSP). Experiments were performed in urethan-anesthetized Long-Evans rats either 4 or 12-16 wk after lesioning. In sham-operated controls, TBS trains ranging from 4 to 12 bursts were sufficient to induce robust LTP [170 +/- 10% (mean +/- SF) of control fEPSP slope; n = 8]. Four-week post -FF-lesioned animals also displayed clear LTP (167 +/- 12% of control fEPSP slope; n = 4) that did not differ from the shams (P > 0.05). In contrast, animals in the 12- to 16-wk post-lesion group showed a highly significant deficit in LTP induction (95 +/- 3% of control fEPSP slope; n = 8; < or =28 burst TBS trains tested; P < 0.001 vs. sham- and 4-wk post-FF-lesion groups). Other quantitative measures of synaptic excitability (i.e., baseline fEPSP slope and input-output relation) did not differ between the sham- and the 12- to 16-wk post-FF-lesion groups. These results indicate that the FF lesion leads to an enduring defect in hippocampal long-term synaptic plasticity that may relate mechanistically to the cognitive deficits characterized in this model.
Li
Chaoying
C
Department of Neuroscience, AstraZeneca CNS Discovery, Wilmington DE 19850-5437, USA. chaoying.li@astrazeneca.com
Maier
Donna L
DL
Cross
Ben
B
Doherty
James J
JJ
Christian
Edward P
EP
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D020712:Fornix, Brain / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000502:physiology*; D013997:Time Factors