Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats

Neuroscience Program, Department of Psychology, Harvard University, William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 01/2005; 20(11):3041-53. DOI: 10.1111/j.1460-9568.2004.03739.x
Source: PubMed


To determine whether the basal forebrain-hippocampal cholinergic system supports sexually dimorphic functionality, male and female Long-Evans rats were given either selective medial septum/vertical limb of the diagonal band (MS/VDB) cholinergic lesions using the neurotoxin 192 IgG-saporin or a control surgery and then postoperatively tested in a set of standard spatial learning tasks in the Morris water maze. Lesions were highly specific and effective as confirmed by both choline acetyltransferase/parvalbumin immunostaining and acetylcholinesterase histochemistry. Female controls performed worse than male controls in place learning and MS/VDB lesions failed to impair spatial learning in male rats, both consistent with previous findings. In female rats, MS/VDB cholinergic lesions facilitated spatial reference learning. A subsequent test of learning strategy in the water maze revealed a female bias for a response, relative to a spatial, strategy; MS/VDB cholinergic lesions enhanced the use of a spatial strategy in both sexes, but only significantly so in males. Together, these results indicate a sexually dimorphic function associated with MS/VDB-hippocampal cholinergic inputs. In female rats, these neurons appear to support sex-specific spatial learning processes.

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    • "Conversely, it's also been shown that hippocampal cholinergic neuron lesions are associated with facilitated learning in a spatial discrimination task [115]. Also, chemical cholinergic blockade in the hippocampus promotes place learning on the Morris water maze [116], and this has been demonstrated in both male and female rats [117] suggesting that the role of hippocampal acetylcholine in spatial learning is not as straightforward as initially thought. Multiple memory systems are also employed by humans to navigate their environment and solve tasks. "
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    ABSTRACT: Studies in both rodents and humans have made much progress in shedding light on how fluctuations in ovarian hormones can affect memory in women across the lifespan. Specifically, advances in neuroscience have identified multiple memory systems that are each mediated by different brain areas. Two memory systems used to navigate an environment are 'place' and 'response' memory. They are defined as either using an allocentric strategy: using a spatial or cognitive map of the surroundings, or an egocentric strategy: using habitual-turns/ movements, respectively. Studies in neuroendocrinology have shown that estrogen levels can bias a female to use one memory system over another to solve a task, such that high estrogen levels are associated with using place memory and low levels with using response memory. Furthermore, recent advances in identifying and localizing estrogen receptors in the rodent brain are uncovering which brain regions are affected by estrogen and providing insight into how hormonal fluctuations during the menstrual cycle, pregnancy, and menopause might affect which memory system is facilitated or impaired in women at different life stages. These studies can help point the way to improving cognitive health in women.
    Full-text · Article · Mar 2014
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    • "This level of self-movement cue processing deficit spares initial response learning in spatial tasks; however, disruptions in performance would be expected on tasks that eliminated environmental cues (i.e., Dark-probe) or place environmental and self-movement cues in conflict (i.e., New-probe). Previous work has shown that infusion of 192-IgG-saporin into the MS/VDB spares place learning in the water maze (Baxter and Gallagher 1996; Jonasson et al. 2004; Vuckovich et al. 2004; Frielingsdorf et al. 2006) and impairs homing accuracy during the Dark-and New-probes of the food-hoarding paradigm (Martin and Wallace 2007). "
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    ABSTRACT: Degeneration of the septohippocampal system is associated with the progression of Dementia of the Alzheimer's type (DAT). Impairments in mnemonic function and spatial orientation become more severe as DAT progresses. Although evidence supports a role for cholinergic function in these impairments, relatively few studies have examined the contribution of the septohippocampal GABAergic component to mnemonic function or spatial orientation. The current study uses the rat food-hoarding paradigm and water maze tasks to characterize the mnemonic and spatial impairments associated with infusing GAT1-Saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). Although infusion of GAT1-Saporin significantly reduced parvalbumin-positive cells in the MS/VDB, no reductions in markers of cholinergic function were observed in the hippocampus. In general, performance was spared during spatial tasks that provided access to environmental cues. In contrast, GAT1-Saporin rats did not accurately carry the food pellet to the refuge during the dark probe. These observations are consistent with infusion of GAT1-Saporin into the MS/VDB resulting in spared mnemonic function and use of environmental cues; however, self-movement cue processing was compromised. This interpretation is consistent with a growing literature demonstrating a role for the septohippocampal system in self-movement cue processing.
    Full-text · Article · Aug 2012 · Brain Structure and Function
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    • "Moreover, the results from the few studies to date, which have examined the effects of biological sex on learning strategy, suggest that the male advantage in spatial performance emerges from a greater reliance on a place learning strategy [50] [51] [52] [53] [54]. However, inconsistencies in results between studies that have employed similar learning paradigms [50] [51] [52] [53], as well as ambiguous learning strategy classification techniques [54], make drawing definitive conclusions about the relationship between biological sex and learning strategy difficult. Therefore, the current study sought to clarify and "
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    ABSTRACT: When learning to navigate toward a goal in a spatial environment, rodents employ distinct learning strategies that are governed by specific regions of the brain. In the early stages of learning, adult male rats prefer a hippocampus-dependent place strategy over a striatum-dependent response strategy. Alternatively, female rats exhibit a preference for a place strategy only when circulating levels of estradiol are elevated. Notably, male rodents typically perform better than females on a variety of spatial learning tasks, which are mediated by the hippocampus. However, limited research has been done to determine if the previously reported male spatial advantage corresponds with a greater reliance on a place strategy, and, if the male preference for a place strategy is impacted by removal of testicular hormones. A dual-solution water T-maze task, which can be solved by adopting either a place or a response strategy, was employed to determine the effects of biological sex and hormonal status on learning strategy. In the first experiment, male rats made more correct arm choices than female rats during training and exhibited a bias for a place strategy on a probe trial. The results of the second experiment indicated that testicular hormones modulated arm choice accuracy during training, but not the preference for a place strategy. Together, these findings suggest that the previously reported male spatial advantage is associated with a greater reliance on a place strategy, and that only performance during the training phase of a dual-solution learning task is impacted by removal of testicular hormones.
    Full-text · Article · Nov 2011 · Physiology & Behavior
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