Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation.

Successful performance of the water maze task requires that rats learn complex behavioral strategies for swimming in a pool of water, searching for and interacting with a hidden platform before its spatial location can be learned. To evaluate whether NMDA receptor-dependent long-term potentiation (NMDA-LTP) is required for learning the required behavioral strategies, rats with NMDA-LTP blocked by systemic pharmacological treatment were trained in the behavioral strategies using simplified and stepwise training methods. Despite the blockade of NMDA-LTP in the dentate gyrus and hippocampal area CA1, rats learned the required behavioral strategies and used them to learn both initial and reversed platform locations. This is the first evaluation of the role of NMDA-LTP specifically in behavioral strategy learning. Although hippocampal NMDA-LTP might contribute to the water maze task, this form of LTP is not essential for learning complex behavioral strategies or multiple hidden platform locations.

Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse.

Using apolipoprotein E knockout mice derived from the Maeda source [Piedrahita J. A. et al. (1992) Proc. natn. Acad Sci. US.A. 89, 4471 4475], we have studied the influence of apolipoprotein E gene deletion on normal CNS function by neurological tests and water maze learning, hippocampal ultrastructure assessed by quantitative immunocytochemistry and electron microscopy, CNS plasticity, i.e. hippocampal long-term potentiation and amygdaloid kindling, and CNS repair, i.e. synaptic recovery in the hippocampus following deafferentation. In each study there was little difference between the apolipoprotein E knockout mice and wild-type controls of similar age and genetic background. Apolipoprotein E knockout mice aged eight months demonstrated accurate spatial learning and normal neurological function. Synaptophysin and microtubule-associated protein 2 immunohistochemistry and electron microscopic analysis of these animals revealed that the hippocampal synaptic and dendritic densities were similar between genotypes. The induction and maintenance of kindled seizures and hippocampal long-term potentiation were indistinguishable between groups. Finally, unilateral entorhinal cortex lesions produced a marked loss of hippocampal synaptophysin immunoreactivity in both groups and a marked up-regulation of apolipoprotein E in the wild-type group. Both apolipoprotein E knockout and wild-type groups showed immunohistochemical evidence of reactive synaptogenesis, although the apolipoprotein E knockout group may have initially shown greater synaptic loss. It is suggested that either apolipoprotein E is of no importance in the maintenance of synaptic integrity and in processes of CNS plasticity and repair, or more likely, alternative (apolipo)proteins may compensate for the loss of apolipoprotein E in the knockout animals.

Fractionating the nonspatial pretraining effect in the water maze task.

Nonspatial pretraining (NSP) enables rats to learn the general strategies of the water maze task (WMT; e.g., learning to swim away from the wall and to climb onto the hidden platform), reduces sensorimotor disturbances, and eliminates acquisition impairments caused by scopolamine hydrobromide, a muscarinic antagonist. To evaluate the contributions of the components of NSP to these effects, NSP was fractionated so that different groups of male rats swam, were placed onto the hidden platform, climbed onto the hidden platform, or were placed into an empty maze before spatial training under scopolamine. No single component of the NSP procedure was sufficient to produce its full effects on sensorimotor disturbances and WMT acquisition. Experience with most or perhaps all of the specific behaviors required in the WMT appears to be important for NSP to produce its full effects.

Fast wave activity in the rat rhinencephalon: elicitation by the odors of phytochemicals, organic solvents, and a rodent predator.

Recent research has shown that bursts of approximately 20 Hz fast waves are elicited in rhinencephalic cortex in rats by the odors of a number of different organic solvents and of components of the secretions of predators such as the weasel and the fox. We now show that a number of phytochemicals (benzyl alcohol, carvacrol, eucalyptol, and salicylaldehyde) will elicit fast wave bursts of about 20 Hz in the rat pyriform cortex. Additional organic solvents (carbon tetrachloride, chloroform, diethyl ether, 1, 2-dimethoxyethane, n-heptane, mesitylene, methylcyclohexane, and commercial gasoline and kerosene, but not N,N-dimethylformamide or dimethyl sulfoxide) and another component of fox secretions (isopentenylmethyl sulfide) were also effective. Many of these compounds will also elicit fast wave bursts of about 20 Hz in the dentate gyrus. The effectiveness of benzyl alcohol, camphor, carvacrol, eucalyptol, isopentenylmethyl sulfide, 2-propylthietane, salicylaldehyde, toluene, and trimethylthiazoline (all of which elicit rhinencephalic fast waves in rats) in suppressing feeding in various small herbivores suggests that the recording of odor-induced rhinencephalic fast waves may provide an easy means of identifying new antifeedants. We found no evidence that the bursts of 20-Hz activity seen in the rat rhinencephalon were kindling-induced seizure-like reactions of the olfactory brain to the vapors of toxic chemicals.