Traumatic brain injury (TBI) is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI.

Specific memory processes and neurological disorders can be ascribed to different dorsoventral regions of the hippocampus. Recently, differences in the anatomical and physiological properties between dorsal and ventral hippocampal CA1 neurons were described for both the rat and mouse hippocampus and have greatly contributed to our understanding of these processes. While differences in the subthreshold properties were similar between rat and mouse neurons, differences in action potential output between dorsal and ventral neurons were strikingly less divergent in mouse compared with rat CA1 neurons. Here, we investigate the mechanism underlying the lack of difference in action potential firing between dorsal and ventral CA1 pyramidal neurons in mouse hippocampus. Consistent with rat, we found that ventral CA1 neurons had a more depolarized resting membrane potential and higher input resistance than dorsal CA1 neurons in the mouse hippocampus. Despite these differences, action potential output in response to current injection was not significantly different. We found that ventral neurons have a more depolarized action potential threshold compared with dorsal neurons and that threshold in ventral neurons was more sensitive to block of KV1 channels compared with dorsal neurons. Outside-out voltage-clamp recordings found that slowly inactivating K+ currents were larger in ventral CA1 neurons. These results suggest that, despite differences in subthreshold properties between dorsal and ventral CA1 neurons, action potential output is normalized by the differential functional expression of D-type K+ channels. NEW & NOTEWORTHY Understanding differences in neurons within a brain region is integral in the reliable interpretation of comparative studies. Our findings identify a novel mechanism by which D-type potassium channels normalize action potential firing between dorsal and ventral CA1 neurons of mouse hippocampus despite differences in subthreshold intrinsic properties. Action potential threshold in ventral neurons is influenced by a greater functional expression of D-type potassium channels resulting in a depolarized action potential threshold compared with dorsal hippocampus.

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in male fmr1 KO mice. Although there were no significant differences in basal synaptic transmission, synaptically evoked dendritic calcium signals were smaller in KO neurons. Using dendritic recording, we found no difference in complex spikes or pharmacologically isolated Ca 21 spikes; however, the threshold for fast, Na 1 -dependent dendritic spikes was depolarized in fmr1 KO mice. Cell-attached patch-clamp recordings found no difference in Na 1 channels between wild-type and fmr1 KO CA1 dendrites. Dendritic spike threshold and TA-LTP were restored by blocking A-type K 1 channels with either 150 mM Ba 21 or the more specific toxin AmmTx3. The impairment of TA-LTP shown here, coupled with previously described enhanced Schaffer collateral LTP, may contribute to spatial memory alterations in FXS. Furthermore, as both of these LTP phenotypes are attributed to changes in A-type K 1 channels in FXS, our findings provide a potential therapeutic target to treat cognitive impairments in FXS.

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in fmr1 KO mice. Furthermore, dendritic Ca2+ influx was smaller and dendritic spike threshold was depolarized in fmr1 KO mice. Dendritic spike threshold and TA-LTP were restored by block of A-type K+ channels. The impairment of TA-LTP coupled with enhanced Schaffer collateral LTP may contribute to spatial memory alterations in FXS. Furthermore, as both of these LTP phenotypes are attributed to changes in A-type K+ channels in FXS, our findings provide a potential therapeutic target to treat cognitive impairments in FXS.