Memory persistence: from fundamental mechanisms to translational opportunities.

Memory persistence is a double edge sword. Persistence of adaptive memories is essential for survival and even determines who we are. Neurodegenerative conditions with significant memory loss such as Alzheimer's disease, testify how defects of memory persistence have severe and irreversible effects on personality, among other symptoms. Yet, maintenance of overly strong maladaptive memories underlies highly debilitating psychiatric conditions including post-traumatic stress disorder, specific phobia, substance dependence and binge eating disorder. Here we review the neurobiological mechanisms supporting memory formation, persistence, inhibition and forgetting. We then shift the focus to how such mechanisms have been exploited to alter the persistence of laboratory-generated memories in human healthy volunteers as a proof of concept. Finally, we review the effect of behavioural and pharmacological interventions in anxiety and addiction disorder patients, highlighting key findings, gaps, and future directions for basic and translational research.

Dorsal striatum coding for the timely execution of action sequences.

The automatic initiation of actions can be highly functional. But occasionally these actions cannot be withheld and are released at inappropriate times, impulsively. Striatal activity has been shown to participate in the timing of action sequence initiation and it has been linked to impulsivity. Using a self-initiated task, we trained adult male rats to withhold a rewarded action sequence until a waiting time interval has elapsed. By analyzing neuronal activity we show that the striatal response preceding the initiation of the learned sequence is strongly modulated by the time subjects wait before eliciting the sequence. Interestingly, the modulation is steeper in adolescent rats, which show a strong prevalence of impulsive responses compared to adults. We hypothesize this anticipatory striatal activity reflects the animals' subjective reward expectation, based on the elapsed waiting time, while the steeper waiting modulation in adolescence reflects age-related differences in temporal discounting, internal urgency states, or explore-exploit balance.

Multielectrode Recordings From Identified Neurons Involved in Visually Elicited Escape Behavior.

A major challenge in current neuroscience is to understand the concerted functioning of distinct neurons involved in a particular behavior. This goal first requires achieving an adequate characterization of the behavior as well as an identification of the key neuronal elements associated with that action. Such conditions have been considerably attained for the escape response to visual stimuli in the crab Neohelice. During the last two decades a combination of in vivo intracellular recordings and staining with behavioral experiments and modeling, led us to postulate that a microcircuit formed by four classes of identified lobula giant (LG) neurons operates as a decision-making node for several important visually-guided components of the crab's escape behavior. However, these studies were done by recording LG neurons individually. To investigate the combined operations performed by the group of LG neurons, we began to use multielectrode recordings. Here we describe the methodology and show results of simultaneously recorded activity from different lobula elements. The different LG classes can be distinguished by their differential responses to particular visual stimuli. By comparing the response profiles of extracellular recorded units with intracellular recorded responses to the same stimuli, two of the four LG classes could be faithfully recognized. Additionally, we recorded units with stimulus preferences different from those exhibited by the LG neurons. Among these, we found units sensitive to optic flow with marked directional preference. Units classified within a single group according to their response profiles exhibited similar spike waveforms and similar auto-correlograms, but which, on the other hand, differed from those of groups with different response profiles. Additionally, cross-correlograms revealed excitatory as well as inhibitory relationships between recognizable units. Thus, the extracellular multielectrode methodology allowed us to stably record from previously identified neurons as well as from undescribed elements of the brain of the crab. Moreover, simultaneous multiunit recording allowed beginning to disclose the connections between central elements of the visual circuits. This work provides an entry point into studying the neural networks underlying the control of visually guided behaviors in the crab brain.