Nongraded amnesia (Spatial memory tasks) Remote memory Hippocampus Neocortex Retrograde amnesia Nongraded amnesia (Spatial memory tasks) Multiple trace theory

methods Physical studies Pharmacological studies Genetic lesion studies Cellular and temporal precise Optogenetics (Opsin Genes)

Specific Optogenetic Inhibition (OGI)of Excitatory Neurons in Dorsal CA1 Reduces Neuronal Activity

A temporally precise, stable and reversible manner

CA1 OGI Blocks Contextual Fear Acquisition and Retrirval A real-time involvement of CA1 excitatory cells, during acquisition and recall

No difference in exploration

Acquisition and expression of fear denpend on the amygdala

CA1 OGI Reversibly Interferes with Remote Fear Memory Recall

Ongoing involvement, default activator of the memory trace

Disturb only recent but not remote OPI limits expression of compensatory mechanisms

Precise but Not Prolonged CA1 OGI Blocks Remote Contextual Fear Recall

Interrupted in the midst of a behavioral session Hippocampus participate in remote memory trace maintenance

Brain-wide Mapping of Circuit Activity Controlled by the Hippocampus during Remote Recall

CA1 recruiting brain-wide fear memory activity Increased activity compensating for hippocampal inactivation

OGI of Anterior Cingulate Cortex (ACC) Inhibits Remote but Not Recent Contextual Memory

Olfactory bulbs (OB), no effect

Point not clear This result at once demonstrates that a sudden drop in a major source of synaptic input to cortex need not nonspecifically influence recall (without ruling out a contribution from such an effect) and also points to the specificity of ACC in remote memory (consistent with prior work).