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A Late Phase of Long-Term Synaptic Depression in Cerebellar Purkinje Cells Requires Activation of MEF2.

Abstract：

:The MEF2 family of transcription factors restricts excitatory synapse number in an activity-dependent fashion during development, yet MEF2 has not been implicated in long-term synaptic depression (LTD), which is thought to initiate synapse elimination. Mutations in MEF2 pathways are implicated in autism spectrum disorders, which include cerebellar dysfunction. Here, we test the hypothesis that cerebellar LTD requires postsynaptic activation of MEF2. Knockdown of MEF2D produces suppression of the transcription-dependent late phase of LTD in cultured Purkinje cells. The late phase of LTD is also completely blocked in Purkinje cells derived from MEF2A+MEF2D null mice and rescued with plasmids that drive expression of MEF2D but not phosphatase-resistant mutant MEF2D S444D. Wild-type Purkinje cells transfected with a constitutively active form of MEF2 show no alterations of synaptic strength. Thus, postsynaptic activation of MEF2 by S444 dephosphorylation is necessary, but not sufficient, for the late phase of cerebellar LTD.

journal_name

Cell Rep

journal_title

Cell reports

authors

Andzelm MM,Vanness D,Greenberg ME,Linden DJ

doi

10.1016/j.celrep.2019.01.004

subject

Has Abstract

pub_date

2019-01-29 00:00:00

pages

1089-1097.e3

issue

5

issn

2211-1247

pii

S2211-1247(19)30004-X

journal_volume

26

pub_type

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