Sensory experience drives long-lasting changes in neural circuit function, which are essential for brain development and learning. A dominant model is that such plasticity involves long-term potentiation (LTP) and depression (LTD), well-studied mechanisms that increase or decrease the strength of synaptic connections between neurons. LTP and LTD are triggered by specific local neural activity patterns according to quantitative synaptic learning rules. Despite an increasing molecular understanding of plasticity, the relevant learning rules driving LTP and LTD in vivo are not known. Work in this proposal will identify these learning rules, in order to allow a quantitative description of how plasticity is induced and how information is stored in neural circuits. The model system is the whisker region of rat somatosensory cortex (S1), which is a classical system for studying the effects of experience on brain function. Whisker deprivation drives LTD at specific S1 synapses. A prospective, model-independent approach will be taken to identify the specific neural activity patterns and learning rules that drive LTD in vivo. The strategy is to record S1 spike trains in awake, behaving rats, and to use quantitative analysis techniques to identify spike train parameters that are altered acutely by deprivation, and that constitute candidate activity patterns that may drive LTD in vivo. These candidate parameters will be played back to neurons in S1 slices in vitro to determine which parameters actually drive LTD, and to characterize the learning rules governing such plasticity. This approach will identify novel learning rules driving plasticity in vivo, and will confirm or reject involvement of previously known rules. Identification of the relevant learning rules for plasticity will provide a critical bridge between existing molecular/synaptic and systems/theoretical descriptions of plasticity and learning. By advancing our understanding of cortical plasticity, this work will suggest new strategies for treating learning disabilities and memory disorders during aging. This work will also support improved instructional techniques in undergraduate education by developing a small-group, discussion-format course to promote critical thinking and reasoning in biology and neuroscience. This course will emphasize structured discussions, critical interactive thinking exercises, and physical demonstrations to teach scientific reasoning skills and promote improved knowledge retention, and will provide an alternative to standard, large-lecture format classes. As part of this effort, graduate students will be intensively trained in interactive, small-group teaching techniques, which will aid their professional development as future educators.
This grant supported neuroscience research addressing how the cerebral cortex of the brain mediates sensation and simple forms of learning. This basic knowledge is necessary to understand how biological systems compute and represent information, and to guide hypotheses for neurological conditions including autism and learning disability impair brain function. We focused on a powerful, widely studied model system, the somatosensory cortex of rodents. In one line of research, we identified the neural code by which the cortex represents tactile (touch) stimuli felt by the whiskers, which are the rodent’s major tactile sensors, analogous to human fingertips. We discovered that whisker stimuli are represented by very sparse but precisely timed action potentials in cerebral cortex. Such ‘sparse coding’ is increasingly recognized as a common motif in cerebral cortex, with important implications for cortical computation and learning. In another line of research, we evaluated a promising candidate learning mechanism termed spike timing-dependent plasticity (STDP), in which the functional strength of synapses is modified based on the precise timing of action potentials. STDP is widely proposed as a basis for associative learning, but whether it occurred in the intact brain was controversial. We demonstrated that STDP occurs in intact brain circuits, and is well suited for information storage in sparsely spiking neural networks. Together, these results provide important information for understanding neural computations and associative learning in mammalian cerebral cortex, and suggest that impairment of sparse coding may be a potential cause of neurological deficits in autism and other disorders. In an education component of this grant, a structured discussion, critical writing, and critical reasoning component was added to large lecture-format biology courses at two universities. The goal was to improve students’ critical thinking and reasoning skills in biology, and to train graduate students in effective discussion-based teaching techniques. This effort was very successful, and is an important broader impact of this grant.
