Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynapticfunctionfor endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesiclesin glutamatergicterminals, anincreasedfrequency of miniature EPSCs, andincreased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory

21. Enhancing Undergraduate Critical Reading Skills in Neuroscience Using Instructor-Developed Study Guides

This study proposes an innovative instructional method for enhancing critical reading skills. Students enrolled in an undergraduate neuroscience course offered at the University of Toronto Scarborough reported that they often experience difficulty in analyzing and interpreting empirical and review journal articles. Our research focuses on student attitudes and perceptions of learning following exposure to instructor-developed study aids based on course readings from various scientific journals. The results of this study can be translated across disciplines to courses that use journal articles as part of the reading requirements, and can further impact course development to better facilitate student learning

Eye-blink conditioning is associated with changes in synaptic ultrastructure in the rabbit interpositus nuclei

Eye-blink conditioning involves the pairing of a conditioned stimulus (usually a tone) to an unconditioned stimulus (air puff), and it is well established that an intact cerebellum and interpositus nucleus, in particular, are required for this form of classical conditioning. Changes in synaptic number or structure have long been proposed as a mechanism that may underlie learning and memory, but localizing these changes has been difficult. Thus, the current experiment took advantage of the large amount of research conducted on the neural circuitry that supports eye-blink conditioning by examining synaptic changes in the rabbit interpositus nucleus. Synaptic quantifications included total number of synapses per neuron, numbers of excitatory versus inhibitory synapses, synaptic curvature, synaptic perforations, and the maximum length of the synapses. No overall changes in synaptic number, shape, or perforations were observed. There was, however, a significant increase in the length of excitatory synapses in the conditioned animals. This increase in synaptic length was particularly evident in the concave-shaped synapses. These results, together with previous findings, begin to describe a sequence of synaptic change in the interpositus nuclei following eye-blink conditioning that would appear to begin with structural change and end with an increase in synaptic number