Selective cholinergic immunolesioning affects synaptic plasticity in developing visual cortex.
Cholinergic neurotransmission is known to affect activity-dependent plasticity in various areas, including the visual cortex. However, relatively little is known about the exact role of subcortical cholinergic inputs in the regulation of plastic events in this region during early postnatal development. In the present study, synaptic transmission and plasticity in the developing visual cortex were studied following selective immunotoxic removal of the basal forebrain cholinergic afferents in 4-day-old rat pups. The lesion produced dramatic cholinergic neuronal and terminal fibre loss associated with decreased mRNA levels for the M1 and M2 muscarinic receptors, as well as clear-cut impairments of long-term potentiation (LTP) in visual cortex slices. Indeed, after theta burst stimulation of layer IV a long-term depression (LTD) instead of an LTP was induced in immunolesioned slices. This functional change appears to be due to the lack of cholinergic input as exogenous application of acetylcholine prevented the shift from LTP to LTD. In addition, lesioned rats showed an increased sensitivity to acetylcholine (ACh). While application of 20 microm ACh produced a depression of the field potential in immunolesioned rat slices, in order to observe the same effect in control slices we had to increase ACh concentration to up to 200 microm. Taken together, our results indicate that deprivation of cholinergic input affects synaptic transmission and plasticity in developing visual cortex, suggesting that the cholinergic system could play an active role in the refinement of the cortical circuitry during maturation.
Kuczewski
N
N
International School for Advanced Studies, Cognitive Neuroscience Sector, Via Beirut 2-4, 34014 Trieste, Italy.
Aztiria
E
E
Leanza
G
G
Domenici
L
L
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000633:toxicity; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000922:Immunotoxins / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009699:N-Glycosyl Hydrolases; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014793:Visual Cortex / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism / Q000473:pathology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D054789:Ribosome Inactivating Proteins, Type 1; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine