Enhanced hippocampal long-term potentiation and spatial learning in aged 11ß-hydroxysteroid dehydrogenase type 1 knock-out mice

Glucocorticoids are pivotal in the maintenance of memory and cognitive functions as well as other essential physiological processes including energy metabolism, stress responses, and cell proliferation. Normal aging in both rodents and humans is often characterized by elevated glucocorticoid levels that correlate with hippocampus-dependent memory impairments. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) amplifies local intracellular ("intracrine") glucocorticoid action; in the brain it is highly expressed in the hippocampus. We investigated whether the impact of 11ß-HSD1 deficiency in knock-out mice (congenic on C57BL/6J strain) on cognitive function with aging reflects direct CNS or indirect effects of altered peripheral insulin-glucose metabolism. Spatial learning and memory was enhanced in 12 month "middle-aged" and 24 month "aged" 11ß-HSD1<sup>–/–</sup> mice compared with age-matched congenic controls. These effects were not caused by alterations in other cognitive (working memory in a spontaneous alternation task) or affective domains (anxiety-related behaviors), to changes in plasma corticosterone or glucose levels, or to altered age-related pathologies in 11ß-HSD1<sup>–/–</sup> mice. Young 11ß-HSD1<sup>–/–</sup> mice showed significantly increased newborn cell proliferation in the dentate gyrus, but this was not maintained into aging. Long-term potentiation was significantly enhanced in subfield CA1 of hippocampal slices from aged 11ß-HSD1<sup>–/–</sup> mice. These data suggest that 11ß-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis

Spatial Representation and Navigation in a Bio-inspired Robot

A biologically inspired computational model of rodent repre-sentation?based (locale) navigation is presented. The model combines visual input in the form of realistic two dimensional grey-scale images and odometer signals to drive the firing of simulated place and head direction cells via Hebbian synapses. The space representation is built incrementally and on-line without any prior information about the environment and consists of a large population of location-sensitive units (place cells) with overlapping receptive fields. Goal navigation is performed using reinforcement learning in continuous state and action spaces, where the state space is represented by population activity of the place cells. The model is able to reproduce a number of behavioral and neuro-physiological data on rodents. Performance of the model was tested on both simulated and real mobile Khepera robots in a set of behavioral tasks and is comparable to the performance of animals in similar tasks

Episodic memory: assessment in animals

Episodic memory has been defined in a way that may make it unique to humans, but an alternative comparative perspective holds that ‘episodic-like memory systems’ occur in animals which are capable of remembering unique events in relation to the contexts in which they occur. Such systems are mediated by circuitry in the medial temporal lobe and its multiple interconnections with cortical and subcortical structures. Specialized features of the neurophysiology of these systems enable animals to remember unique events in a context-specific manner, to recall sequences of events, and to distinguish remembering from merely recognizing stimuli they have seen before

The memory paradox

Declarative and emotional memories are key to quality of life and day-to-day functioning. The absence of memory or the inability to recall memories properly in an emotional context leads to dysfunction but, paradoxically, memories that generate too much emotion can be equally disabling

Hippocampal representation in place learning

The generality of the place-learning impairment associated with hippocampal system damage was challenged using methods of training that permitted subjects to form an individual association between the place of escape and a particular navigational route in an open-field water maze. Both normal rats and rats with fornix lesions (FX rats) acquired this task rapidly, although FX rats were slightly slower in achieving minimum escape latencies. In postcriterion testing, FX rats occasionally made near misses but, more often, their escape performance was indistinguishable from that of intact rats. Results from a variety of probe tests indicated that FX rats, like normal rats, had based their performance on a representation of multiple distal cues but their representation, unlike that of normal rats, was inflexible in that it could not be used to guide performance when the cues o