Sexually dimorphic effects of hippocampal cholinergic deafferentation in rats

Authors

  • Zachariah Jonasson,

    1. Neuroscience Program, Department of Psychology, Harvard University, William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
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  • Jonathan F. X. Cahill,

    1. Neuroscience Program, Department of Psychology, Harvard University, William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
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  • Rachel E. Tobey,

    1. Neuroscience Program, Department of Psychology, Harvard University, William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
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  • Mark G. Baxter

    1. Neuroscience Program, Department of Psychology, Harvard University, William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
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Dr Zachariah Jonasson, as above.
E-mail: jonasson@wjh.harvard.edu

Abstract

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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