The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 
pathway is involved in many cellular processes, including cell growth and 
differentiation, immune functions and cancer. It is activated by various 
cytokines, growth factors, and protein tyrosine kinases (PTKs) and regulates the 
transcription of many genes. Of the four JAK isoforms and seven STAT isoforms 
known, JAK2 and STAT3 are highly expressed in the brain where they are present 
in the postsynaptic density (PSD). Here, we demonstrate a new neuronal function 
for the JAK/STAT pathway. Using a variety of complementary approaches, we show 
that the JAK/STAT pathway plays an essential role in the induction of 
NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus. 
Therefore, in addition to established roles in cytokine signaling, the JAK/STAT 
pathway is involved in synaptic plasticity in the brain.