An Schreurs

Distinct Properties of Long-Term Potentiation in the Dentate Gyrus along the Dorsoventral Axis: Influence of Age and Inhibition

The hippocampus is important for spatial navigation, episodic memory and affective behaviour. Increasing evidence suggests that these multiple functions are accomplished by different segments along the dorsal-ventral (septal-temporal) axis. Long-term potentiation (LTP), the best-investigated cellular correlate of learning and memory, has distinct properties along this axis in the CA1 region, but so far, little is known about longitudinal differences in dentate gyrus (DG). Therefore, here we examined potential dorsoventral differences in DG-LTP using in vitro multi-electrode array recordings. In young mice, we found higher basal synaptic transmission in the dorsal DG, while the LTP magnitude markedly increased towards the ventral pole. Strikingly, these differences were greatly reduced in slices from middle-aged mice. Short-term plasticity, evaluated by paired-pulse ratios, was similar across groups. Recordings in the presence and absence of GABAA-receptor blocker picrotoxin suggested a higher inhibitory tone in the ventral DG of young mice, confirmed by an increased frequency of miniature inhibitory postsynaptic currents. Our findings support the view that the hippocampus contains discrete functional domains along its dorsoventral axis and demonstrate that these are subject to age-dependent changes. Since these characteristics are presumably conserved in the human hippocampus, our findings have important clinical implications for hippocampus- and age-related disorders.

Single mild traumatic brain injury results in transiently impaired spatial long-term memory and altered search strategies

&NA; Mild traumatic brain injury (mTBI) can lead to diffuse neurophysical damage as well as cognitive and affective alterations. The nature and extent of behavioral changes after mTBI are still poorly understood and how strong an impact force has to be to cause long‐term behavioral changes is not yet known. Here, we examined spatial learning acquisition, retention and reversal in a Morris water maze, and assessed search strategies during task performance after a single, mild, closed‐skull traumatic impact referred to as “minimal” TBI. Additionally, we investigated changes in conditioned learning in a contextual fear‐conditioning paradigm. Results show transient deficits in spatial memory retention, which, although limited, are indicative of deficits in long‐term memory reconsolidation. Interestingly, minimal TBI causes animals to relapse to less effective search strategies, affecting performance after a retention pause. Apart from cognitive deficits, results yielded a sub‐acute, transient increase in freezing response after fear conditioning, with no increase in baseline behavior, an indication of a stronger affective reaction to aversive stimuli after minimal TBI or greater susceptibility to stress. Furthermore, western blot analysis showed a short‐term increase in hippocampal GFAP expression, most likely indicating astrogliosis, which is typically related to injuries of the central nervous system. Our findings provide evidence that even a very mild impact to the skull can have detectable consequences on the molecular, cognitive and affective‐like level. However, these effects seemed to be very transient and reversible. HighlightsA mouse model for weak, single mild traumatic brain injury (minimal TBI) is used.Minimal TBI results in transient deficits in long‐term memory reconsolidation.Minimal TBI causes relapse to less effective search strategies in the water maze.Minimal TBI leads to a transient increase in freezing during fear conditioning.A transient rise in hippocampal GFAP after minimal TBI indicates astrogliosis.