Spatial reference memory and neocortical neurochemistry vary with the estrous cycle in C57BL/6 mice.

Estrous cycle-related variations of spatial reference memory and neurochemistry in intact female mice were examined. Spatial reference memory was tested in cycling females, ovariectomized (OVX) females, and males by using a 1-day water maze protocol. Choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were measured in the hippocampus and neocortex. Estrus females exhibited worse spatial acquisition and 30-min retention than did proestrus and metestrus females, higher neocortical ChAT activity than proestrus females, and higher neocortical GAD activity than OVX females and males. Neocortical, rather than hippocampal, neurochemistry was more sensitive to hormonal modulation, suggesting that hormonal mediation of neocortical function may play a critical role in regulating spatial reference memory in female mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neonatal monoaminergic depletion in mice (Mus musculus) improves performance of a novel odor discrimination task

This experiment examined behavior and neurochemistry in adult mice (Mus musculus) after neonatal depletion of monoaminergic fibers projecting to the neocortex and hippocampus. Lesions were made on Postnatal Day 1; mice developed to adulthood and were assessed on simple odor discrimination (SOD) and odor delayed nonmatch-to-sample (DNMS) tasks, passive avoidance (PA), and locomotor activity. On SOD, lesioned mice performed faster than controls but with similar accuracy. On the DNMS task, the lesioned mice performed faster and more accurately than controls. On PA, the lesioned mice exhibited a retention deficit relative to controls. Locomotor activity was similar in the 2 groups. Postmortem analyses revealed that the lesions reduced significantly norepinephrine and serotonin levels in both the neocortex and hippocampus. The data suggest that cortically projecting monoaminergic fibers play an important role in normal cognitive development.     

Different effects of postnatal day 1 versus 7 192 immunoglobulin G-saporin lesions on learning, exploratory behaviors, and neurochemistry in juvenile rats.

Passive avoidance learning and retention, as well as locomotor and exploratory behaviors, were assessed in rats after intraventricular 192 immunoglobulin G-saporin injections on either Postnatal Day 1 (PND1) or PND7. PND1-lesioned rats were not significantly impaired on acquisition or retention of passive avoidance. PND7-lesioned rats acquired the task slower than controls, but retention was not affected. PND7-lesioned rats were less exploratory than controls and showed reduced wall rearing. Histological analysis of PND1- and PND7-lesioned rats revealed no neuronal degeneration in hippocampus or cortex. There was a marked reduction of choline acetyltransferase (ChAT) activity in the hippocampus, cortex, and septum in the PND7-lesioned rats and a slight but significant ChAT depletion in the cortex of PND1-lesioned rats. These data suggest that the cholinergic system is critical for the learning of passive avoidance and exploratory behavior in the developing rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of carbon dioxide-induced anesthesia on cholinergic parameters in rat brain

We report that acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities in rat brain were virtually identical whether the rat was anesthetized with carbon dioxide (CO2) before decapitation or decapitated without prior sedation. The AChE and ChAT activities were measured in three brain regions: the hippocampus, cerebral cortex, and cerebellum. Enzyme activities varied significantly by brain region, with the highest values in the hippocampus and the lowest values in the cerebellum. Enzyme activities, however, did not vary with the method of euthanasia, either CO2-induced anesthesia prior to decapitation or decapitation without anesthesia. These data suggest that CO2-induced anesthesia prior to decapitation does not alter activities of these cholinergic markers in rat hippocampus, cerebral cortex, and cerebellum. This method of euthanasia eliminates the need to capture a conscious animal, which reduces stress to the animal and the experimenter.     

Postnatal choline supplementation in preweanling mice: Sexually dimorphic behavioral and neurochemical effects.

The aim of this study was to investigate the effects of postnatal choline supplementation on neurochemical and behavioral parameters in preweanling BALB/cByJ mice. Mouse pups were injected daily subcutaneously with choline chloride (0.85 mM/g body weight) from Postnatal Day (PND) 1 to PND 16. Pups performed a passive avoidance (PA) learning task on PND 17-18 and a 30-min locomotor activity test on PND 19. The choline treatment affected retention of the PA task on PND 18. The treatment also increased locomotor activity in females, but not in males, on PND 19. Choline acetyltransferase (ChAT) enzymatic activity was measured on PND 20 and revealed that choline administration in the first 2 weeks of postnatal life selectively affects male pups. Choline's effect, as seen in previous rat experiments, was to decrease ChAT activity in the hippocampal region. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexually dimorphic effects of anti-NGF treatment in neonatal rats

To investigate the sensitivity to changes in excitability of motoneuron pool dependent on voluntary motor commands, we recorded motor evoked potentials (MEPs) and H-reflexes from the right flexor carpi radialis (FCR) muscle of normal human subjects. Amplitudes of MEPs were always larger than those of the H-reflex in both tonic and phasic muscle contractions. Furthermore, amplitudes of MEP and H-reflex were larger in phasic than in tonic muscle contraction. These results indicate that there are differences in the sensitivity to changes in motoneuronal excitability related to the production of excitatory postsynaptic potentials for H-reflex and MEP responses, respectively.     

Sexually dimorphic responses to neonatal basal forebrain lesions in mice: II. Cortical morphology

Previous studies in the mouse have shown that neonatal lesions to the cholinergic basal forebrain (nBM) areas result in transient cholinergic depletion of neocortex and precipitate altered cortical morphogenesis. Lesion-induced morphological alterations in cortex persist into adulthood and are accompanied by behavioral changes, including spatial memory deficits. The current study investigated whether neonatal nBM lesions affect male and female mice differently in adulthood. Quantitative morphometry of cortical layer width was employed to assess alterations in cytoarchitecture in neonatally nBM-lesioned and littermate control mice of both sexes following behavioral testing. Our results showed significant decreases in cortical layer IV and V widths across somato/motor cortex in neonatally nBM lesioned mice of both sexes. Sexually dimorphic responses were observed in cortical layer II/III and total cortical width, limited to the area containing the "barrel cortex" representation of the whisker hairs. In lesioned females, layer II/III and total cortical width were decreased relative to female controls, and in lesioned males, layer II/III was increased relative to controls, whereas total cortical width was unchanged. In male but not female mice we observed significant correlations between decreased widths in layer IV and V and impaired performance on a spatial memory task. The current data further support a role of developing cholinergic cortical afferents in the modulation of cortical morphogenesis and cortical circuits involved in cognitive behaviors. In addition, our observations provide further evidence for sexually dimorphic development and function in cognitive centers of the rodent brain.     

Sex differences in learning and memory in mice: Effects of sequence of testing and cholinergic blockade.

Sexual dimorphism in spatial and cued navigation using the Morris water maze was examined in C57BL/6 mice both with and without administration of scopolamine, a cholinergic blocker. In Exp 1, female and male mice learned to perform first a spatial, then a cued, navigation task. Both performed a spatial task similarly; males, however, performed a cued task better than females. In Exp 2, the sequence of navigation testing was reversed. Both performed similarly on a cued task; however, males performed a spatial task better than females. In both experiments, females were more sensitive than males to the effects of scopolamine. No significant confounding sex differences were found in either spontaneous activity or passive avoidance retention. These data indicate that sex differences in spatial and cued tasks are dependent on the sequence of task presentation and implicate a role for the cholinergic system in these differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry

The nucleus basalis magnocellularis (nBM) provides the primary source of cholinergic input to the cortex. Neonatal lesions of the nBM produce transient reductions in cholinergic markers, persistent abnormalities in cortical morphology, and spatial navigation impairments in adult mice. The present study examined sex differences in the effects of an electrolytic nBM lesion on postnatal day 1 (PND 1) in mice on behavior and neurochemistry in adulthood. Mice were lesioned on PND 1 and tested at 8 weeks of age on a battery of behavioral tests including passive avoidance, cued and spatial tasks in the Morris water maze, simple and delayed nonmatch to sample versions of an odor discrimination task, and locomotor activity measurements. Following behavioral testing, mice were sacrificed for either morphological assessment or neurochemical analysis of a cholinergic marker or catecholamines. There were no lesion or sex differences in acquisition or retention of passive avoidance, performance of the odor discrimination tasks, or activity levels. Control mice showed a robust sex difference in performance of the spatial water maze task. The lesion produced a slight cued but more dramatic spatial navigation deficit in the water maze which affected only the male mice. Neurochemical analyses revealed no lesion-induced changes in either choline acetyltransferase activity or levels of norepinephrine or serotonin at the time of testing. The subsequent report shows a sex difference in lesion-induced changes in cortical morphology which suggests that sexually dimorphic cholinergic influences on cortical development are responsible for the behavioral deficits seen in this study.     

Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.

The role of the developing cholinergic basal forebrain system on cognitive behaviors was examined in 7 day-old rats by giving lesions with intraventricular injections of 192 IgG-saporin or saline. Rats were subjected to passive avoidance on postnatal days (PND) 22–23, water maze testing on PND 50–60, and a open-field test (in which reactions to spatial and object novelty were measured) on PND 54. Behavioral effects of the lesions were evident only in the open-field test with 5 objects. Unlike controls, the lesioned rats did not detect a spatial change after a displacement of 2 of the 5 objects. Control and lesioned rats, however, showed comparable novelty responses to an unfamiliar object. Lesion effectiveness was confirmed by 75% and 84% decreases in choline acetyltransferase activity in cortex and hippocampus. These results suggest that the developing cholinergic system may be involved in spatial information processing or attention to spatial modifications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)