FEAR MEMORY TRACE

Cellular mechanisms underlying formation of the fear memory trace in the mouse amygdala

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 Obiettivo del progetto (Objective)

'Conditioned fear memory in response to an auditory stimulus serves as a prototype for studying the pathological emotional states as well as understanding the neural mechanisms of memory allocation, storage, retrieval and extinction. The conditioned fear memory in mice has been found to be allocated and stored within a subgroup of neurons in the amygdala, a critical region for expression of this type of memory. Expression levels of the transcription factor CREB (cyclic adenosine 3’-5’ monophospate response element –binding protein) has been shown to modulate allocation of memory to a specific group of neurons, constituting the memory trace, and neuronal excitability could play a role. Our goals in this proposal are, first, to investigate the synaptic properties in pairs of LA neurons before and after fear conditioning, and second, to delineate the neural mechanisms that allow a neuron to encode a specific memory and become part of the memory trace. In approaching our goals, we will conduct electrophysiological experiments in mice transfected with viral vectors that co-express CREB tagged with the green fluorescent protein (GFP) and the gene for channelrhodopsin2 (ChR2) allowing for specific activation of the transfected neurons. We will study the synaptic properties in pairs of transfected neurons by stimulating one neuron with a laser and performing whole-cell patch clamp recordings in another one. In addition, we will construct a network of amygdala neuron models based on experimental data which will allow us to simulate the emergence of plasticity changes observed in neurons that encode the same memory, and study the underlying biophysical mechanisms of these plasticity changes. The results from behavioral, electrophysiological and modeling experiments will give us insights on how neurons compete with each other for allocation to a specific memory.'

Introduzione (Teaser)

Memory and behavioural conditioning

Descrizione progetto (Article)

Memory allocation is a process where neurons and synapses in a biological neural network process information to form a memory trace. The amygdala is the part of the brain that is associated with development of fear memories. The project 'Cellular mechanisms underlying formation of the fear memory trace in the mouse amygdala' (FEAR MEMORY TRACE) studied the amygdala neural network to elucidate their role in fear memory formation.

In vivo genetic manipulation, behavioural, electrophysiological and computational approaches were used to elucidate the underlying biophysical mechanisms involved in fear conditioning and taste aversion.

The researchers received training to conduct behavioural and electrophysiological experiments and test for short- and long-term memory. Skills required included performing intra-amygdala surgeries, patch-clamp recording, molecular and cellular analysis using western blot, genotyping, and viral DNA preparation as well as computational simulations.

Behavioural testing revealed an enhanced fear memory performance at the three hour time point rather than at five hours. Electrophysiological readings were taken after auditory fear conditioning and conditioned taste aversion at three hour and five hour time-points. Data revealed that after three hours, there was higher intrinsic excitability in mice who received both the shock and the tone as compared to those that received only the tone. The scientists simulated the learning-induced physiological changes seen during conditioning using models from constructed from the experimental data.

Currently, electrophysiological recordings in brain slices are still ongoing in combination with fluorescence imaging. A behavioural facility has been set-up successfully to test memory and record anxiety as well as locomotor activity.

Project activities promise to reveal the underlying biophysical mechanisms involved in behavioural conditioning and memory trace formation. This knowledge could be exploited to treat memory deficits and psychological conditions such as phobias through memory manipulation. This has important implications for the public health sector.