Pten and EphB4 regulate the establishment of perisomatic inhibition in mouse visual cortex.
Perisomatic inhibition of pyramidal neurons is established by fast-spiking, parvalbumin-expressing interneurons (PV cells). Failure to assemble adequate perisomatic inhibition is thought to underlie the aetiology of neurological dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we show that in mouse visual cortex, strong perisomatic inhibition does not develop if PV cells lack a single copy of Pten. PTEN signalling appears to drive the assembly of perisomatic inhibition in an experience-dependent manner by suppressing the expression of EphB4; PV cells hemizygous for Pten show an ∼2-fold increase in expression of EphB4, and over-expression of EphB4 in adult PV cells causes a dismantling of perisomatic inhibition. These findings implicate a molecular disinhibitory mechanism driving the establishment of perisomatic inhibition whereby visual experience enhances Pten signalling, resulting in the suppression of EphB4 expression; this relieves a native synaptic repulsion between PV cells and pyramidal neurons, thereby promoting the assembly of perisomatic inhibition.
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Amy
A
Baohan
Department of Anatomy &Neurobiology, UCI, Irvine, California 92697, USA.
Taruna
T
Ikrar
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Elaine
E
Tring
Department of Anatomy &Neurobiology, UCI, Irvine, California 92697, USA.
Xiangmin
X
Xu
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Joshua T
JT
Trachtenberg
D000818:Animals; D004622:Embryo, Mammalian; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D008027:Light; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017966:Pyramidal Cells; D036224:Receptor, EphB4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014793:Visual Cortex / Q000502:physiology*
D010320:Parvalbumins; C086681:Ephb4 protein, mouse; D036224:Receptor, EphB4; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse