The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons remains elusive. Using transgenic mice conditionally expressing a dominant-negative CREB (CREBS133A: mCREB) mutant, we found that inhibiting CREB function does not alter spine density, spine morphology, and levels of polymerized actin in naive CA1 neurons. CREB inhibition, however, impaired contextual fear conditioning and produced a learning-induced collapse of spines associated with a blockade of learning-dependent increase in actin polymerization. Blocking mCREB expression with doxycycline rescued memory and restored a normal pattern of learning-induced spines, demonstrating that CREB controls structural adaptations of neurons selectively involved in memory formation.
Silvia Middei; Alida Spalloni; Patrizia Longone; Christopher Pittenger; Shane M. O'Mara; Hélène Marie; Martine Ammassari-Teule
We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, w ... more
In Aplysia, repeated trials of aversive stimuli produce long-term sensitization (LTS) of defensive reflexes and suppression of feeding. Whereas the cellular underpinnings of LTS have been characterized, the mechanisms of feeding suppression remained unknown. Here, we report that LTS traini ... more
The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C–Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role ... more
The human mouth is home to a teeming community of microbes, yet still relatively little is known about what determines the specific types of microorganisms that live there. Is it your genes that decide who lives in the microbial village, or is it your environment? In a study published in ... more
Your genes determine much about you, but environment can have a strong influence on your genes even before birth, with consequences that can last a lifetime. In a study published in Genome Research, researchers have for the first time shown that the environment experienced in the womb defi ... more
The human gut is home to a teeming ecosystem of microbes that is intimately involved in both human health and disease. But while the gut microbiota is interacting with our body, they are also under constant attack from viruses. In a study published in Genome Research, researchers have ana ... more