Synaptic plasticity deficits in an experimental model of XXXX : long-term potentiation saturation and its pharmacological reversal.

@entity154 @entity20217 @entity19 @entity73 @entity6694 @entity3393 @entity4778 @entity143 @entity2848
@entity6694 ( @entity6694 ), a disorder caused almost exclusively by mutations in the X-linked gene, @entity20217 , has a phenotype thought to be primarily of neurological origin. Disruption of @entity20217 in @entity19 results in a prominent @entity6694 -like phenotype. One of the consequences of @entity20217 absence in the brain is altered functional and structural plasticity. We aimed to characterize synaptic effects related to plasticity in the hippocampus further and establish whether @entity154 are amenable to pharmacological reversal. Using male @entity19 in which @entity20217 expression was prevented by a stop cassette, we assessed synaptic plasticity in area @entity4778 at different phenotypic stages, scoring the @entity19 weekly for overt @entity6694 -like signs. Strongly symptomatic @entity20217 (stop/y) @entity19 displayed reduced long-term potentiation (LTP, 40.2  1.6% of wild-type), post-tetanic potentiation (PTP, 45  18.8% of wild-type) and paired-pulse facilitation ( @entity2848 , 78  0.1% of wild type) (all P<0.05), the impairment increasing with symptom severity score. These @entity73 were absent in presymptomatic @entity19 . Repeated high frequency stimulation revealed pronounced LTP saturation in symptomatic @entity20217 (stop/y) @entity19 , suggesting an LTP 'ceiling' effect. Bath application of the weak @entity143 receptor blocker @entity3393 (1  M) resulted in partial restoration of a short-term plasticity component. These data support that idea that progressive functional synaptic impairment is a key feature in the @entity6694 brain and demonstrate the potential for the pharmacological restoration of plasticity function.
