Browsing by Author "Faress, Islam"

Memory formation is one of the most important brain capacities. Memories shape our personalities and modulate our behaviour to adapt to the environment. Experience-dependent enhancement of synaptic efficacy in the form long-term potentiation (LTP) is widely accepted as the basis of memory formation and storage. Memory storage is a dynamic process and memories have different life-times. Salient experiences are encoded as long-term memories (LTMs), while insignificant events are encoded as short-term memories (STMs) that we can recall temporarily before they decay. However, these trivial events become more memorable if they occur before or after a salient event that is encoded as an LTM. A leading hypothesis of cellular-memory consolidation, the synaptic tagging and capture (STC) hypothesis might offer a mechanistic explanation for the strengthening phenomenon of transient-memories. The STC asserts that in a two-pathway setup, where two neurons converge onto the same postsynaptic neuron, an induction of an early-LTP (E-LTP), weak and temporary, on one input, can be stabilized into a late-LTP (L-LTP), strong and long-lasting, if it is preceded or followed by a heterosynaptic L-LTP on the other convergent input. The cumulative evidences indicate that E-LTP and L-LTP model STM and LTM formation, respectively. The STC hypothesis has been well-established at the neuronal level via in-vivo and in-vitro studies, but, it has not been validated in behaving animals employing associative memories. The work presented here aims at establishing a methodology for testing the predictions of the STC hypothesis at the behavioural level with circuit- and synapse-specific manipulations. For this purpose, auditory fear-conditioning was chosen as behavioural paradigm because it is well studied at the molecular, the synaptic and the circuit scale. Since the STC hypothesis explains synaptic events and memory formation occurs at the level of the synapses, optogenetics was utilized in this study because it is a powerful method that provides high spatiotemporal resolution for manipulating synaptic activity with light. The final-study design involves encoding an STM in the form of E-LTP at thalamic-inputs to the lateral amygdala. This is carried out by pairing optical stimulation of presynaptic terminals with an aversive stimulus, a foot-shock. An application of an optical L-LTP on the independent and convergent cortical-inputs is expected to transform the thalamic-STM into an LTM, according to the STC predictions. To this end, I demonstrated optogenetically -for the first time- that pairing the presynaptic activation of the thalamic inputs with a foot-shock is sufficient for encoding an associative fear-memory. Two proof-of-concept experiments were executed afterward to investigate the suitability of the proposed study design. Firstly, by attenuating the intensity of the aversive stimulus, I examined the possibility of encoding a thalamic-STM which lasts less than 24 hours. Secondly, to ensure that the proposed design could allow for specific examination of the heterosynaptic consolidation of the thalamic-STM, I investigated the potential confounding-effect of homosynaptic L-LTP. The results indicate that homosynaptic consolidation might indeed be a confounder that interferes with testing the STC predictions. Consequently, further investigations with a bigger sample size will be carried out to test the statistical significance of the observed effects and eliminate the confounding factors that might interfere with the behavioural validation of the STC theory.