Aging is associated with impairments in learning and memory and a greater incidence of limbic seizures. These changes in the aged brain have been associated with increased excitability of hippocampal pyramidal cells caused by a reduced number of GABAergic interneurons. To better understand these issues, we performed cell counts of GABAergic interneurons and examined GABA efflux and GABAergic inhibition in area CA1 of the hippocampus of young (3-5 mo) and aged (26-30 mo) rats. Aging significantly reduced high K + /Ca 2+ -evoked GABA, but not glutamate efflux in area CA1. Immunostaining revealed a significant loss of GABAergic interneurons, but not inhibitory boutons in stratum oriens and stratum lacunosum moleculare. Somatostatinimmunoreactive oriens-lacunosum moleculare (O-LM) cells, but not parvalbumin-containing interneurons were selectively lost. O-LM cells project to distal dendrites of CA1 pyramidal cells, providing dendritic inhibition. Accordingly, inhibition of dendritic input to CA1 from entorhinal cortex was selectively reduced. These findings suggest that the age-dependent loss of interneurons impairs dendritic inhibition and dysregulates entorhinal cortical input to CA1, potentially contributing to cognitive impairment and seizures.

Aging is associated with many physiological alterations—such as changes in sleep patterns, metabolism and food intake—suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3–4 months) and old (26–28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances.

Native tone language experience has been linked with alterations in the production and perception of pitch in language, as well as with the brain response to linguistic and non-linguistic tones. Here we use two experiments to address whether these changes apply to the discrimination of simple pitch changes and pitch intervals. Event related potentials (ERPs) were recorded from native Mandarin speakers and a control group during a same/different task with pairs of pure tones differing only in pitch height, and with pure tone pairs differing only in interval distance. Behaviorally, Mandarin speakers were more accurate than controls at detecting both pitch and interval changes, showing a sensitivity to small pitch changes and interval distances that was absent in the control group. Converging evidence from ERPs obtained during the same tasks revealed an earlier response to change relative to no-change trials in Mandarin speakers, as well as earlier differentiation of trials by change direction relative to controls. These findings illustrate the cross-domain influence of language experience on the perception of pitch, suggesting that the native use of tonal pitch contours in language leads to a general enhancement in the acuity of pitch representations.

Several lines of evidence point to a role for the hippocampal formation and contiguous temporal lobe structures in a variety of learning and memory paradigms. Presumably, these cognitive phenomena are mediated (and accompanied) by dynamic changes in neurochemical transmission that may differ between learning and recall phases. However, the neurotransmitter correlates of most memory-related tasks have not been thoroughly investigated. Here we used a one-trial object recognition paradigm paired with in vivo microdialysis to assess hippocampal acetylcholine (ACh), glutamate and GABA efflux when rats were exposed to familiar objects, and when given the option to explore familiar and novel objects. Rats preferentially explored the novel object over the familiar one when presented with the option. Regardless of object familiarity, object exploration was accompanied by an increase in hippocampal ACh efflux, while GABA efflux was unaffected. However, glutamate efflux was not increased above baseline levels by presentation of familiar objects, but was significantly enhanced in the presence of the novel object. These data suggest that the hippocampus, and in particular, hippocampal glutamate, may be involved in memory processes during novelty recognition paradigms.

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