In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.

The retrosplenial cortex is strongly connected with brain regions involved in spatial signaling. To test whether it also codes space, single cells were recorded while rats navigated in an open field. As in earlier work (L. L. Chen, L. H. Lin, C. A. Barnes, & B. L. McNaughton, 1994; L. L. Chen, L. H. Lin, E. J. Green, C. A. Barnes, & B. L. McNaughton, 1994), the authors found head direction cells with properties similar to those in other areas. These cells were slightly anticipatory. Another cell type fired to particular combinations of location, direction, and movement, which suggested that they may fire whenever the rat approaches a particular location, using a particular locomotor behavior. The remaining cells could not be clearly categorized but also showed a significant correlation with one or more of the spatial-movement variables examined. The fact that the retrosplenial cortex contains spatial and movement-related signals and is connected with the motor cortex suggests that it may play a role in path integration or navigational motor planning.

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We recorded head direction (HD) cells from the lateral mammillary nucleus (LMN) and anterior thalamus (ATN) of freely behaving rats and also made bilateral lesions of LMN while recording HD cells from ATN. We discovered that the tuning functions of LMN HD cells become narrower during contraversive head turns, but not ipsiversive head turns, compared to when the head is not turning. This narrowing effect does not occur for ATN HD cells. We also found that the HD signal in LMN leads that in ATN by about 15-20 ms. When LMN was lesioned bilaterally, HD cells in ATN immediately lost their directional firing properties and never recovered them. Based on these findings, we argue that LMN may be an essential component of an attractor-integrator network that participates in generating the HD signal.