Silencing KCC2 in mouse dorsal hippocampus compromises spatial and contextual memory

Simonnet, Clémence; Sinha, Manisha; Goutierre, Marie; Moutkine, Imane; Daumas, Stéphanie; Poncer, Jean Christophe

doi:10.1038/s41386-022-01480-5

Cited by 3 publications

(1 citation statement)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such mechanism is the shift in neuronal intracellular chloride concentration from high to low via the mature expression of KCC2. Notably, KCC2-deficient mice exhibit similar pathologies of breathing abnormalities, lower body mass and impaired cognition and memory to those of MECP2 models [ 274 , 275 , 276 ]. In Rett syndrome, KCC2 levels are altered in patients, neurons derived from patient induced pluripotent stem cells and the MECP 2 model [ 178 , 188 , 277 , 278 , 279 ], with suggestions that KCC2 is downstream of MECP2 [ 280 ], or reduced MECP2 -influenced BDNF signalling [ 281 , 282 , 283 ] suppresses KCC2 [ 284 ], which is reduced in patient neurons derived from induced pluripotent stem cells [ 278 ].…”

Section: Inhibitory Influences On Rett Syndromementioning

confidence: 99%

Inhibitory Synaptic Influences on Developmental Motor Disorders

Fogarty

2023

IJMS

View full text Add to dashboard Cite

During development, GABA and glycine play major trophic and synaptic roles in the establishment of the neuromotor system. In this review, we summarise the formation, function and maturation of GABAergic and glycinergic synapses within neuromotor circuits during development. We take special care to discuss the differences in limb and respiratory neuromotor control. We then investigate the influences that GABAergic and glycinergic neurotransmission has on two major developmental neuromotor disorders: Rett syndrome and spastic cerebral palsy. We present these two syndromes in order to contrast the approaches to disease mechanism and therapy. While both conditions have motor dysfunctions at their core, one condition Rett syndrome, despite having myriad symptoms, has scientists focused on the breathing abnormalities and their alleviation—to great clinical advances. By contrast, cerebral palsy remains a scientific quagmire or poor definitions, no widely adopted model and a lack of therapeutic focus. We conclude that the sheer abundance of diversity of inhibitory neurotransmitter targets should provide hope for intractable conditions, particularly those that exhibit broad spectra of dysfunction—such as spastic cerebral palsy and Rett syndrome.

show abstract