Synapse-to-nuclear trafficking of

CRTC1 in neurons
The task of hippocampus calls for retrieval,
processing short-term memory and transferring
memory from short term to longer delay periods.

CRTC1 nuclear translocation; LTP

 Synapse-to-Nucleus Translocation
of CRTC1 in Organotypic Slice Cultures
and Acute Hippocampal Slice Preparations
 Synapse-to-Nucleus Translocation of
CRTC1 in Hippocampal Neurons

Experiment using local glutamate uncaging followed by CRTC1

immunocytochemistry indicate that the loss of CRTC1 is confined to the
stimulated dendrite
CRTC1 in the glutamate uncaged = CRTC1 in adjacent control dendrite
 Nuclear Translocation of CRTC1 Requires
Activation of Calcineurin; cAMP Regulates the
Persistence of CRTC1 in the Nucleus

• Hippocampal cultures were pretreated with CsA (5 mM) for 4 hr

prior to a 1 hr stimulation with bicuculline (BIC; 40 mM) or with
forskolin (FSK; 25 mM).
• Neurons were fixed and immunostained with antibodies against
MAP2 (red), CRTC1 (green), and Hoechst nuclear dye (blue,
merged),

ANALYSIS: ELEVATED intracellular cAMP in ABSENCE of neuronal activity

does not trigger CRTC1 nuclear translocation.
NO NUCLEAR IMPORT

BUT cAMP ALLOWS CRTC1 to stay within nucleus

 Synapse to neuron translocation
bZIP
• May contribute to specificity of CREB-dependent
transcriptional responses domain
• CRTC1 translocation could preserve spatial information
about initial site of stimulation
• TRANSCRIPTION at nucleus:
• CREB required at LATE STAGE LTP
• CREB –phosphorylation by PKA and Ca++/calmodulin protien
kinases
Secondary messenger cascades causes this spatial information
to be lost
• Stimuli triggering loss of CRTC1 from stimulating synapses
provides that spatial Information
NATURE OF STIMULATION REQUIRED FOR LONG TERM
SYNAPTIC EFFICACY

CREB PROTEIN DNA BINDING

 STIMULUS acting through neuromodulators like
norepinephrine, dopamine at hippocampus following
strong tetanic stimulation enhances long-term memory
formation.

Different CRTC1-dependent gene expression trigger

distinct types of CREB-dependent memory