title: Effects of D-AP5 and NMDA microiontophoresis on associative learning in the barrel cortex of awake rats.
abstract: Experiments involving single-unit recordings and microiontophoresis were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61 cells. In 23 cases, there was no other manipulation whereas in the remaining 38, pairing occurred in the presence of one of three pharmacological agents previously shown to modulate learning, receptive field plasticity and long-term potentiation: N-methyl-D-aspartic acid (NMDA) (n=8), the NMDA receptor antagonist AP5 (n=17) or the nitric oxide synthase inhibitor L-nitro-arginine-N-methyl-ester (L-NAME) (n=13). Non-associative (unpaired) experiments (n=14) and delivery of pharmacological agents without pairing (n=14) served as controls. Changes in neuronal responsiveness to S1 following one of these procedures were calculated and adjusted relative to changes in the responses to S2. On average, whisker pairing alone yielded a 7% increase in the responses to S1. This enhancement differed significantly from the 17% decrease obtained in the non-associative control condition and could not be attributed to variations in the state of the animals because analysis of the cervical and facial muscle electromyograms revealed that periods of increased muscular activity, reflecting heightened arousal, were infrequent (less than 4% of a complete experiment on average) and occurred randomly. The enhancement of the responses to S1 was further increased when whisker pairing was performed in the presence of L-NAME (27%) or NMDA (35%) whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both neuronal excitability and responsiveness to S1 whereas AP5 depressed them. However, the effects of both substances disappeared immediately after administration had ended. L-NAME did not affect the level of ongoing activity and responses to S1 significantly. From these data, we concluded that, since the changes in the responses to S1 lasted longer than the periods of both whisker pairing and drug delivery, they were not residual excitatory or inhibitory drug effects on neuronal excitability. Thus, our results indicate that, relative to the unpaired controls, whisker pairing led to a 24% increase in the responsiveness of barrel cortex neurons to peripheral stimulation and that these changes were modulated by the local application of pharmacological agents that act upon NMDA receptors and pathways involving nitric oxide. We can infer that somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing.
authors.affiliation: Département de Physiologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Maalouf
authors.forename: R W
authors.initials: RW
authors.lastname: Dykes
authors.forename: A A
authors.initials: AA
authors.lastname: Miasnikov
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D004576:Electromyography; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007478:Iontophoresis / Q000379:methods*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009474:Neurons / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D014738:Vibrissae / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester