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      Neuroscientists as Cartographers: Mapping the Crossroads of Gonadal Hormones, Memory and Age Using Animal Models

      1 , 2 , * , 1 , 2 , 1 , 2

      Molecules

      MDPI

      estrogen, progesterone, androgens, cognition, aging

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          Abstract

          Cognitive function is multidimensional and complex, and research in multiple species indicates it is considerably impacted by age and gonadal hormone milieu. One domain of cognitive function particularly susceptible to age-related decrements is spatial memory. Gonadal hormones can alter spatial memory, and they are potent modulators of brain microstructure and function in many of the same brain areas affected by aging. In this paper, we review decades of animal and human literature to support a tertiary model representing interactions between gonadal hormones, spatial cognition and age given that: 1) gonadal hormones change with age, 2) age impacts spatial learning and memory, and 3) gonadal hormones impact spatial learning and memory. While much has been discovered regarding these individual tenets, the compass for future aging research points toward clarifying the interactions that exist between these three points, and understanding mediating variables. Indeed, identifying and aligning the various components of the complex interactions between these tenets, including evaluations using basic science, systems, and clinical perspectives, is the optimal approach to attempt to converge the many findings that may currently appear contradictory. In fact, as discoveries are being made it is becoming clear that the findings across studies that appear contradictory are not contradictory at all. Rather, there are mediating variables that are influencing outcome and affecting the extent, and even the direction, of the effects that gonadal hormones have on cognition during aging. These mediating variables are just starting to be understood. By aligning basic scientific discoveries with clinical interpretations, we can maximize the opportunities for discoveries and subsequent interventions to allow individuals to “optimize their aging” and find their own map to cognitive health as aging ensues.

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          Most cited references 317

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          Microstructure of a spatial map in the entorhinal cortex.

          The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.
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            Place navigation impaired in rats with hippocampal lesions

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              A cortical-hippocampal system for declarative memory.

               H. Eichenbaum (2000)
              Recent neurobiological studies have begun to reveal the cognitive and neural coding mechanisms that underlie declarative memory--our ability to recollect everyday events and factual knowledge. These studies indicate that the critical circuitry involves bidirectional connections between the neocortex, the parahippocampal region and the hippocampus. Each of these areas makes a unique contribution to memory processing. Widespread high-order neocortical areas provide dedicated processors for perceptual, motor or cognitive information that is influenced by other components of the system. The parahippocampal region mediates convergence of this information and extends the persistence of neocortical memory representations. The hippocampus encodes the sequences of places and events that compose episodic memories, and links them together through their common elements. Here I describe how these mechanisms work together to create and re-create fully networked representations of previous experiences and knowledge about the world.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                31 August 2010
                September 2010
                : 15
                : 9
                : 6050-6105
                Affiliations
                [1 ]Department of Psychology, Arizona State University, Tempe, AZ 85287, USA
                [2 ]Arizona Alzheimer’s Consortium, Phoenix, AZ 85006, USA; E-Mails: Jazmin.Acosta@ 123456asu.edu (J.I.A.); jtalboom@ 123456asu.edu (J.S.T.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: bimonte.nelson@ 123456asu.edu ; Tel.: +1-480-727-0766; Fax: +1-480-965-8544.
                Article
                molecules-15-06050
                10.3390/molecules15096050
                3126862
                20877209
                © 2010 by the authors;

                licensee MDPI, Basel, Switzerland. This article is an Open Access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

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                estrogen, progesterone, androgens, cognition, aging

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