Actin cytoskeleton and memory formation


It has been shown that fear learning leads to changes in neuronal synaptic transmission and morphology in brain areas underlying fear memory formation including the amygdala and hippocampus. The actin cytoskeleton has been shown to be involved in such key neuronal processes. We and others revealed that actin polymerization in rat amygdala is needed for fear memory consolidation (Mantzur et al., 2009). Furthermore, several actin-regulatory proteins have been shown to be involved in fear memory formation. For example, inhibition of the Rho GTPase effector the Rho-associated kinase (ROCK), a kinase that affects actin cytoskeleton, in lateral amygdala impaired the formation of long- but not short-term fear memory formation (Lamprecht et al., (2002). Neuron, 36, 727-38). Profilin is another actin cytoskeleton-regulatory protein that regulates actin polymerization by promoting the elongation of F-actin by funneling ATP-actin to the growing actin filament. Fear conditioning in rats leads to the movement of profilin into dendritic spines in the lateral amygdala (Lamprecht et al., (2006). Nat Neurosci. 9, 481-3). Profilin containing spines were shown to be larger compared to spines that do not contain profilin. A greater proportion of profilin-containing spines with enlarged PSDs could contribute to the enhancement of associatively induced synaptic responses in the lateral amygdala following fear learning.



AMPA receptor and memory formation


Long-term memory formation is believed to involve alterations of synaptic efficacy. It has been shown that GluA1-containing AMPA receptors are inserted into synapses following stimuli leading to plasticity and that GluA2/GluA3-containing receptors replace existing synaptic AMPA receptors continuously and may act to maintain synaptic efficacy. Insertion and maintenance of AMPA receptors in synapse depends on interaction with intracellular proteins. We show that GluA2-NSF interaction in lateral amygdala is necessary for fear memory consolidation but not retrieval or persistence (Joels and Lamprecht, (2010). J Neurosci 30:15981-6). The membrane proximal region (MPR) of AMPA receptor (AMPAR) is needed for receptor trafficking and synaptic plasticity. We show that  the MPR region of GluA1 is essential for acquisition of memory, whereas the MPR region of GluA4 is essential for long-term fear memory formation (Ganea et al., Neuropsychopharmacology (2015)).   



The roles of Eph receptors and ephrins in memory formation


Evidence indicates that long-term memory (LTM) formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrins ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptors conductance and trafficking, synaptic glutamate reuptake and dendritic spines morphogenesis. We demonstrated that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders (Dines and Lamprecht, Translational Psychiatry, (2014)).


Laboratory for Molecular Neurobiology of Memory