ABSTRACT
Activity dependent calcium entry into neurons can initiate a form of synaptic plasticity called long-term potentiation (LTP). This phenomenon is considered by many to be one possible cellular mechanism underlying learning and memory. The calcium entry that induces this phenomenon can occur when N-methyl-D-aspartate receptors (NMDARs) and/or voltage-dependent calcium channels (VDCCs) are activated. While much is known about synaptic plasticity and the mechanisms that are triggered by activation of these two Ca(2+) channels, it is unclear what roles they play in learning. To better understand the role activation of these channels may play in learning we systemically administered pharmacological antagonists to block NMDARs, VDCCs, or both during training trials and retention tests in a radial arm maze task. Wistar rats injected with the NMDAR antagonist MK-801 (0.1mg/kg) were impaired in the acquisition of this task. In contrast, rats injected with verapamil (10mg/kg), an antagonist to VDCCs, acquired the task at the same rate as control animals, but were impaired on a 10-day retention test. A group of animals injected with both antagonists were unable to learn the task. The results suggest that each of the calcium channels and the processes they trigger are involved in a different stage of memory formation or expression.
Subject(s)
Calcium Channels/drug effects , Maze Learning/drug effects , Receptors, N-Methyl-D-Aspartate/drug effects , Retention, Psychology/drug effects , Space Perception/drug effects , Spatial Behavior/drug effects , Animals , Behavior, Animal/drug effects , Dizocilpine Maleate/administration & dosage , Dizocilpine Maleate/pharmacology , Injections , Male , Memory/drug effects , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Neuropsychological Tests , Rats , Rats, WistarABSTRACT
This experiment explores the role of two forms of long-term potentiation (LTP) in behavioral memory. NMDA and/or voltage-dependent calcium channels (VDCCs) were antagonized pharmacologically at levels that block nmdaLTP and vdccLTP, respectively, in rats learning an eight-arm radial maze task. Animals were trained twice a day for 11 d under the systemic influence of MK-801, verapamil, both drugs, or saline. During acquisition, the mixed drug group displayed significantly more working memory errors and reference memory errors than all other groups. The mixed drug group was markedly impaired on the first daily trial but improved dramatically on their second daily trial. After a 7 d delay, saline and MK-801 animals maintained their predelay level of performance. The performance of the verapamil groups declined significantly over the delay. These results demonstrate that: (1) vdccLTP is necessary for the retention of information over a 7 d period, (2) the blockade of both forms of LTP prevents the retention of information over a 21 hr period, and (3) blockade of both forms of LTP does not prevent the storing of information over a short period of time (3 hr).
