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Introduction: Fragile X messenger ribonucleoprotein (FMRP) is a protein involved in many neuronal processes in the nervous system including the modulation of synaptic transmission. The loss of FMRP produces the fragile X syndrome (FXS), a neurodevelopmental disorder affecting synaptic and neuronal function and producing cognitive impairments. However, the effects of FXS on short-term processing of synaptic inputs and neuronal outputs in the hippocampus have not yet been sufficiently clarified. Furthermore, it is not known whether dorsal and ventral hippocampi are affected similarly or not in FXS. Method: We used an Fmr1 knockout (KO) rat model of FXS and recordings of evoked field potentials from the CA1 field of transverse slices from both the dorsal and the ventral hippocampi of adult rats. Results: Following application of a frequency stimulation protocol consisting of a ten-pulse train and recordings of fEPSP, we found that the dorsal but not ventral KO hippocampus shows altered short-term synaptic plasticity. Furthermore, applying the frequency stimulation protocol and recordings of population spikes, both segments of the KO hippocampus display altered short-term neuronal dynamics. Conclusions: These data suggest that short-term processing of synaptic inputs is affected in the dorsal, not ventral, FXS hippocampus, while short-term processing of neuronal output is affected in both segments of the FXS hippocampus in a similar way. These FXS-associated changes may have significant impact on the functions of the dorsal and ventral hippocampi in individuals with FXS. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder characterized by intellectual disability and is related to autism. FXS is caused by mutations of the fragile X messenger ribonucleoprotein 1 gene (Fmr1) and is associated with alterations in neuronal network excitability in several brain areas including hippocampus. The loss of fragile X protein affects brain oscillations, however, the effects of FXS on hippocampal sharp wave-ripples (SWRs), an endogenous hippocampal pattern contributing to memory consolidation have not been sufficiently clarified. In addition, it is still not known whether dorsal and ventral hippocampus are similarly affected by FXS. We used a Fmr1 knock-out (KO) rat model of FXS and electrophysiological recordings from the CA1 area of adult rat hippocampal slices to assess spontaneous and evoked neural activity. We find that SWRs and associated multiunit activity are affected in the dorsal but not the ventral KO hippocampus, while complex spike bursts remain normal in both segments of the KO hippocampus. Local network excitability increases in the dorsal KO hippocampus. Furthermore, specifically in the ventral hippocampus of KO rats we found an increased effectiveness of inhibition in suppressing excitation and an upregulation of α1GABAA receptor subtype. These changes in the ventral KO hippocampus are accompanied by a striking reduction in its susceptibility to induced epileptiform activity. We propose that the neuronal network specifically in the ventral segment of the hippocampus is reorganized in adult Fmr1-KO rats by means of balanced changes between excitability and inhibition to ensure normal generation of SWRs and preventing at the same time derailment of the neural activity toward hyperexcitability. [ABSTRACT FROM AUTHOR]