Examination of neocortical plasticity during forebrain-dependent trace-associative learning tasks

Learning;Memory;Structural Plasticity;Synapses;Neocortex

Chau, Lily

关键词: Learning;    Memory;    Structural Plasticity;    Synapses;    Neocortex;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/46622/Lily_Chau.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Classic studies utilizing general learning and memory tasks, such as environmental enrichment and acrobatic training paradigms, have robustly demonstrated increased neocortical dendritic spine density following various types of general learning.Though these studies have been instrumental in revealing experience-induced and general learning-induced plasticity, the timing of the anatomical and molecular modifications underlying these general learning and memory tasks (as well as the specific type of learning involved with these changes) are difficult to pinpoint.To date, neocortical plasticity at different time points of a more specific learning and memory task, such as associative learning, has not been closely examined.One associative learning task that is suitable to examine neocortical modifications during different time points of learning is trace-eyeblink conditioning.During eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) (i.e., tone or whisker deflection) paired with a salient, unconditioned stimulus (US) (i.e., mild periorbital eyeshock) to elicit an unconditioned response (UR) (i.e., eyeblink).With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) (i.e., eyeblink) when presented with the CS.In trace conditioning, there is a stimulus free interval between the CS and the US.Acquisition for trace conditioning is forebrain-dependent because it requires an intact neocortex and hippocampus (Solomon et al., 1986; Moyer et al., 1990; Kim et al., 1995; Weiss et al., 1999a; Takehara et al., 2002; Galvez et al., 2007).Using the trace-eyeblink conditioning paradigm with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have demonstrated that primary somatosensory cortex (barrel cortex) is required for WTEB conditioning acquisition and retention (Galvez et al., 2007).Additionally, findings have demonstrated that this trace-associative learning results in an expansion of the cytochrome oxidase stained representation for the conditioned whisker barrels in layer IV of primary somatosensory cortex (Galvez et al., 2006; Galvez et al., 2011; Chau et al., 2013a).Together, these findings demonstrate that WTEB conditioning is a suitable task to examine neocortical anatomical and molecular modifications at different time points of trace-associative learning.Furthermore, findings from these studies demonstrate that acquisition for this trace-association results in neocortical cytochrome oxidase plasticity; however, the underlying modifications for this trace-association are unknown.Based upon the previously mentioned findings demonstrating experience-induced synaptic modifications, one possible cause for the increase in metabolic activity following WTEB conditioning is synaptic modification.Findings from Chapter 2 demonstrating increased synapsin I expression, a presynaptic marker, in the conditioned barrels following WTEB conditioning support that synaptic modifications occur following learning.Closer examination of learning-induced synaptic modifications in Chapter 3 demonstrating transient spine proliferation during WTEB conditioning suggests that learning results in structural plasticity, or neocortical rewiring, that is time-dependent.Furthermore, findings from Chapter 5 demonstrating a similar timeline for transient up-regulation of calcium-related and synapse-related genes during the acquisition phase strongly suggest that the changes in these calcium-related and synapse-related genes are underlying the transient learning-induced structural plasticity.Additionally, findings from Chapter 4b and Chapter 6 demonstrate learning-induced plasticity in other areas of the brain that have been shown to play pivotal roles in learning and memory, such as the amygdala.Collectively, findings from this dissertation suggest that multiple brain regions work in synchrony to establish and fine-tune new connections during learning.