The Related Pathways And Mechanism Of Training-Induced Plasticity In Auditory Cortex

Hubel and wiesel revealed the effect of visual experience on ocular dominance columns in the1960, researchers have been coming into notice that how neuronal architecture and connectivity were shaped by experience in the way that impact their physiology and behavior. Lots of studies have shown that sensory experience and learning could produce the plasticity of sensory brain cortex. Recently, the mechanism underlie experience-dependent plasticity has been widely concerned. However, the laminar profiles of training-induced changes are not well understood, although the research in changes of the physiological properties of neurons induced by experience in the cortex have made great progress. Here, auditory thalamocortical slice was obtained to understand the pathway of the projects from thalamus to cortex and the distribution of neurons in primary auditory cortex. Then we want to know the effect of behavioral training on the laminar profile in trained adult rats. Finally, the mechanism was addressed underlie intensive auditory training.This dissertation including three chapters as follows:Chapter1Auditory thalamocortical pathwayAcoustic information via thalamus is integrated and processed in auditory. Studies in anatomy and physiology have demonstrated that thalamic afferents arrive in layer4(L4), whose neurons project to L2and L3. Axonal projections of pyramidal cells in these layers terminate in L5and some of those from L5in L6. Brander et al. study showed that the forward afferents from thalamus determine the tonotopic organization. Although lots of anatomic and physiological evidences, cellular and synaptic mechanism by which thalamic inputs are transmitted to and processed in ACx are little know. Depite some progress has been made in intracellular recordings in vivo, the difficulty of the precision of electrophysiology and pharmacology still exist. The application of brain-slice preparation provides an ideal environment to do research in intracellular recording and pharmacology. The auditory thalamocortical brain slice maintains an intact auditory thalamocortical pathway enable researcher to facilitate similar progress in the understanding of auditory forebrain mechanisms.Here, mice were use to obtain thalamocortical brain, which contained main ventral of medial geniculate (MGv) and primary auditory cortex and intact forward thalamocortical afferents. Responses were evoked in auditory cortex by MGv stimulation. The result showed that the connection between MGv and primary auditory cortex has strict "zone" model that is the stimulation of MGv could produced responses in a small zone, but the fast and strongest response only in certain point located in middle layer. Also, the position of fast and strongest response would relocate as the position of MGv stimulation was moved, but the response was still in middle layer. This result suggested that projects from thalamus to the middle layer in primary auditory cortex determine the strict tonotopic organization.Finally, nicotine was used to test functional properties of auditory thalamocortical brain slice. Result showed the nicotine enhanced the responses in all layers, which confirmed our hypothesis that this primary thalamocortical slice was functional connection between MGv and primary auditory cortex. The primary slice will provide useful tools to the investigate mechanism of information processing and pharmacological studies in auditory cortex.Chapter2Auditory-cued training strengthens intracortical pathways in primary auditory cortex that mediate response to the rewarded toneThe effect of auditory training on the plasticity in auditory cortex has been widely reported since1990s. Earlier studies in auditory cortex has shown that have shown that training dependent changes in primary auditory map organization after training monkey on a frequency discrimination task. Monkeys significantly improved to discriminate different frequencies after several weeks of behavioral training. Weinberger and colleagues revealed another type of training induced cortical plasticity. Classical conditioning (CS+) induced frequency-specific receptive field (RF) plasticity, which characterized as a shift in the best frequencies in the direction of the frequency of the CS+, and decreased responses to most other frequencies.These studies suggest that auditory training induced plasticity in A1. However, the training-induced plasticity would be different in early and late life. Several studies demonstrated that passive sensory experience influenced the tonotopic organization and electrophysiological properties during critical period. In later life, such plasticity is slower and more limited in adults, except when stimuli are behaviorally relevant. In this study, tone-detection task was used to train rats to get food rewards. The tonotopic organization analysis in primary auditory cortex show that5kHz tone detection training resulted in the5kHz characteristic frequency (CF) representation in A1was expanded while the-10kHz representation significantly reduced relative to naive control rats.In the first chapter, the functional thalamocortical brain slice was obtained and showed main thalamic afferents arrive at layer4, whose neurons project to layer2/3. Here, current-source density (CSD) was used to analyze laminar profiles in A1. Our goal was to determine the laminar profile of changes near the expanded5kHz regions by determining "CSD receptive fields," and infer changes to thalamocortical and/or intracortical inputs.After mapping, we then placed a16-channel silicon multiprobe in middle-(-10kHz) and high-(-20kHz) CF regions and obtained current-source density (CSD) profiles evoked by a range of tone stimuli (CF±1-3octaves in0.25octave steps). Our goal was to determine the laminar profile of changes near the expanded5kHz region by determining "CSD receptive fields," and infer changes to thalamocortical and/or intracortical inputs. Behavioral training altered CSD receptive fields at the10kHz, but not20kHz, site. At the10kHz site, current sinks evoked by a5kHz tone (the target stimulus) were enhanced in layer2/3, but not layer4, and the bandwidth of the layer2/3current sink RF was increased; these results imply training-induced plasticity along intracortical pathways. The layer4current sink receptive field was not clearly separable into thalamocortical and intracortical components, but the results implied lesser, if any, changes to thalamocortical inputs. Finally, we related behavioral performance (d') to CSD changes in individual animals, and found a strong correlation between d'on the final day of training and the amplitude of the5kHz-evoked current sink in layer2/3(r2=0.763).The prediction of behavioral performance by the target-evoked layer2/3current sink suggests that this intracortical pathway is important for brain plasticity underlying learning.Chapter3Intensive training in adults refines auditory discrimination degraded in early life and alters expression of GABAA subunits and GluR2in auditory cortexPerceptual training has important role in the functionally development in the auditory cortex. In this chapter, rats were trained to examine whether discrimination degraded in early life could be recovered by intensive sound-azimuth spatial training. Then western blotting were used to investigate mechanism underlie learning.Rat pups were raised in the presence of continuous and moderate level pulsed noise during critical period. At postnatal35, go/no-go the sound-azimuth spatial strategy was used to train rats and control rats for approximate4weeks. Behavioral results have shown that the time course for noise-reared rats to master the behavior was30-35days, which was remarkable more than control group that was10-12days. The results indicated the that intensive spatial target training significantly improved behavioral performing for noise-reared animals even though it took a longer time to catch up the same level as the control animals. Further more, western blotting was used to examine the changes of the inhibitory and excitatory receptor. Then results showed that the pulse-noise exposure resulted in decreasing the expression of the GABAA receptor a1subunit, AMPA receptor GluR2subunit and GABAA receptor β2and GABAA receptor (33subunit. However, the expression of GABAA receptor a3increased. More important, we found that intensive spatial training in adulthood would result in a return expression level as the control adult animals. The results further demonstrate the perceptual training, as a strategy functional would normalize the deteriorated auditory cortex in adults in the basis of molecular mechanisms.