g., growth factor regulation,

MAPK signaling, and epigenetic mechanisms, are conserved in the adult CNS to subserve long-term plasticity and memory formation (Ehninger et al., 2008, Marcus Obeticholic Acid et al., 1994 and Weeber and Sweatt, 2002). That cellular development and adult memory are molecular homologs, i.e., share identical molecular and biochemical mechanisms, provides an explanation for one of the long-standing questions in neuroscience: why can’t neurons divide? One of the critical roles for most adult neurons is to be plastic: to be able to modulate their function over time. Moreover, in many instances the cellular changes need to be either long-lasting or permanent in order for the neuron to serve the appropriate

function in a given neural circuit. The terminally differentiated adult neuron has adapted many of the molecular mechanisms used to regulate cell division and perpetuate cell phenotype in order to perform one of its primary functions, long-term plasticity. These processes can therefore no longer be utilized to trigger cell division or alter cell phenotype. Ribociclib The authors wish to thank Tom Carew, Huda Zoghbi, Art Beaudet, and Eric Kandel for many helpful discussions. Research in the authors’ laboratory is supported by funds from the NINDS, NIMH, NIA, NIDA, the Rett Syndrome Foundation, the Ellison Medical Foundation, and the Evelyn F. McKnight Brain Research Foundation. “
“Learning to fear threats in the environment is highly adaptive; it allows animals, whether

rats or humans, to anticipate harm and organize appropriate defensive behaviors in response to threat (Bolles, 1970, Fanselow and Lester, 1988 and Ohman and Mineka, 2001). However, this form of learning can also lead to pathological fear memories that fuel disorders of and fear and anxiety, such as panic disorder and post-traumatic stress disorder (PTSD) in humans (Bouton et al., 2001, Rasmusson and Charney, 1997 and Wolpe and Rowan, 1988). What determines an individual’s vulnerability to developing pathological fear after a traumatic experience is not clear; simply experiencing trauma does not appear to be sufficient (Jovanovic and Ressler, 2010 and Yehuda and LeDoux, 2007). Less than 10% of individuals that experience a traumatic event, such as a natural disaster, will develop symptoms of PTSD. Nonetheless, in those individuals that develop PTSD, an important clinical concern is how to limit pathological fear once it has been established (Powers et al., 2010 and Rothbaum and Davis, 2003). Yet limiting pathological fear is a considerable challenge insofar as fear memories are evolutionarily programmed to be rapidly acquired, temporally enduring, and broadly generalized across both familiar and novel contexts.