Experience-Dependent Plasticity Of Multisensory Integration Of Cat Superior Collicular Neurons

Animals receive different sensory information through different sensory systems. For example, the brain receives the visual and auditory information which is firstly encoded by the relative sensory apparatuses then conducted through the respective afferent pathway. However, the external events and stimuli are often composed of multiple sensory cues, which require the brain to be capable of synthesizing the different sensory inputs to reflect the nature of them. Much less is known about how the brain integrates the different modality sensory inputs. Cat SC provides the ideal place for such research, wherein multiple sensory inputs converging into the deep layer leads to the high proportion distribution of multisensory neurons. SC multisensory neurons play the pivotal role in the processes of the integration of the multiple sensory information and the sensory-motor integration, which is believed to increase the likelihood of detecting and identifying events or objects of interest.In the past more than 30 years, the multisensory integration in the nervous system was well examined and some fundamental integrative principles were extracted. Much attention was paid to the importance of information integration in the brain by more and more scientists, and many of them even joined this research field. Despite this, it must be said that we know little about multisensory integration in the neural system. Some questions are listed below.One: What kinds of sensory experience are of particular importance for the development of multisensory integration while the previous studies demonstrated acquirement of the multisensory integration capability was dependent on the sensory experience? An example is provided that if a naive auditory-visual multisensory neuron tries to develop its auditory-visual multisensory integration capability, what kind of sensory experience is needed, visual, auditory, unpaired auditory-visual or paired auditory-visual experience?Two: We know that multisensory neurons received more than one modality-specific sensory input. We did not know whether / how different sensory channels influence with each other? Three: Whether or not multisensory integrative principles can be altered by the particular sensory experience since that is so critical to the multisensory integration?The purpose of my research is to explore these fundamental and meaningful issues of the neural system. The research was conducted on the three different fields, which focused on the sensory - dependent plasticity of the multisensory system.Chapter 1: Initiating the Development of Multisensory Integration by Manipulating Sensory ExperienceThe studies in the cats and monkeys reported that multisensory integration was not an innate characteristic of SC neurons. Acquirement of multisensory integration is sensory dependent. The evidence from the dark reared cats showed that multisensory neurons failed to integrate cross-modal stimuli and response to the cross-modal stimuli was not significantly better than response to the more effective component stimulus. We wonder whether sensory experience could craft the multisensory neurons in dark reared cat SC to develop the ability to integrate the cross-modal stimuli? The experiment was conducted in five adult dark reared cats (postnatal months: 7-11). A recording chamber was stereotaxically placed over a craniotomy to provide access to the SC via the overlying cortex and attached to the skull.Weekly recording sessions began after a postsurgical recovery period of at least 7 days. After anesthesized and paralyzed, the animal was fixed in the stereotaxic apparatus. Different animals were exposed to different stimulus configurations. Two animals (Cat 1 and Cat 2) were exposed to spatiotemporally coincident visual and auditory stimuli (i.e., cross-modal stimuli) at a 6s interstimulus-interval (3hrs/day). Other two animals (Cat 3 and Cat 4) were given the exposure to these same visual stimulus and auditory stimulus for the same number of iterations in these same spatial locations, but with interleaved presentation of these modality-specific stimuli. The fifth animal (Cat 5) was also exposed to these modality-specific stimuli, but in spatial-temporal random way.The result demonstrated that multisensory experience rather than unisensory experience drove the developing of the multisensory integration. The data obtained from the Cat1 and Cat2 demonstrated that multisensory neurons' integrative capability gradually enhanced with the accumulation of multisensory experience. Although a couple of multisensory neurons rapidly developed the multisensory integration capability after only experienced with the quite shorted-term period of cross-modal exposure (2-3 sessions: 3600-5400 trials), the acquirement of mature multisensory integration capability was found to need a large number of cross-modal stimuli exposure trials (more than 27000 exposure trials). The key experiential factor was repeated exposure to the relevant stimuli, and this required that the multiple receptive fields of a multisensory neuron encompass the cross-modal exposure site. Simple exposure to the individual components of a cross-modal stimulus was ineffective in this regard. Furthermore, once a neuron acquired multisensory integration capabilities at the exposure site, it generalized this experience to other locations, albeit with lowered effectiveness.The present data showed that multisensory integration can develop only after experience with multisensory experience. One of the speculations is that long-term repeated cross-modal stimuli shifted the balance between excitatory and inhibitory interaction of different sensory inputs, with the decrement of the mutual inhibition and the enhancement of the mutual facilitation. Also, there was high likelihood that acquirement of multisensory integration was the consequence of the formation of new synapses and the construction of new neural circuits. Our results provided the critical experimental evidence for curing the patients with incapability of multisensory integration and for recovering the multisensory integration capability of patients with brain injury.Chapter 2: Short-term Exposure to Cross-modal Stimuli Increased the Effectiveness of Modality-specific StimulusMultisensory neurons fuse the different sensory inputs to yield the robust multisensory response. What is the impact on the individual sensory channels afforded by this integrative product? Here we will examine this quite critical but always neglected issue. Multisensory neurons and unisensory neurons coexisted in cat SC. We believe that some proportion of unisensory neurons may be the potential multisensory neurons due to that the unisensory response was modulated by the presentation of another modality stimulus.Here we found that after the experience with short-term cross-modal exposure, nearly one third of unisensory neurons studied became multisensory neurons and the spike response was evoked by the stimulus in the initially silent sense. For example, the neuron initially viewed as the auditory neuron yielded the spike response to the visual stimulus after the short-term period of auditory-visual stimuli exposure. Newly evoked responses were characterized by the low magnitude. Most of them could last for more than 20 min. 8 unisensory neurons, unexpectedly, begin to respond to the stimulus in the silent modality after repeatedly exposed to the effective modality-specific stimulus. Despite that, it was obvious that cross-modal exposure has more effectiveness in activating "the silent modality" than the effective modality-specific exposure. The magnitude of evoked response from the new activated modality was better and the retaining time lasted longer following cross-modal exposure than following the modality-specific exposure. We also explored that the impact of cross-modal training on the multisensory neurons. This experiment was conducted in the 48 multisensory neurons. The result showed that cross-modal exposure would enhance the effectiveness of modality-specific stimulus (especially for initial weak effective stimulus) so that the same modality-specific stimulus could evoke the robust response after the exposure. The magnitude of the response was increased and the interstimulus interval was shortened and the response variability was decreased.Our research results revealed the important influence of multisensory integration on sensory channels that multisensory integration could enhance the efficacies of sensory channels. Hebbian LTP mechanism / STDP (Spike timing dependent plasticity) may underlie it. Considering the enhancement of spontaneous firing rate after cross-modal exposure, change in the neuronal excitatory state induced by the cross-modal exposure and modality-specific exposure, was also likely to engage in this process. Chapter 3: Adult plasticity in multisensory neurons: Short-term experience-dependent changes in the superior colliculusMultisensory neurons can integrate the cross-modal stimuli presented in space and time proximity. When the longer SOA (Stimulus onset asynchrony) was used, the multisensory neuron was incapable of synthesizing the cross-modal stimuli and the responses evoked by the different stimuli were separated temporally. We wonder whether this situation can be changed by the sensory experience.The experiment was conducted on the three cats. After a multisensory neuron was isolated, the response properties were examined and the SOA was determined. Repeated sequential cross-modal exposure training (50-80 trials) was given. It was found that neurons rapidly adapted its response to this stimuli configuration. This short-term plasticity was evident as a rapid increase in the magnitude and duration of responses to the first stimulus, and a shortening of the latency and increase in magnitude of the responses to the second stimulus when they are presented in sequence. The result was that the two responses appeared to merge. These changes were stable in the absence of experience with competing stimulus configurations, outlasted the exposure period, and could not be induced by equivalent experience with sequential within-modal (visual-visual or auditory-auditory) stimuli.The results showed that multisensory neurons in adult Cat SC can rapidly adapt information processing capabilities to deal with the environmental change so that multisensory integration can take place in the extensive range of the cross-modal stimuli configuration. In addition, if the sequential presentation of the cross-modal stimuli is treated as a miniature event, neurons seems to be able to encode the context, which may represent the way in which high cognitive level of neural system encode the similar event. STDP (Spike Timing Dependent Plasticity) theoretical model at least partly provides the explanation of the present results. According to this model, the second response could provide the preceding stimuli with the feedback supporting during training, which results in the enhancement of the response to the preceding stimulus. Multisensory neurons' capability of integrating the cross-modal stimuli was likely to be another important support. However, if both components of the sequential stimuli are the same modality, the sensory channel afforded by the facilitation and inhibition due to the sharing the same or most of sensory channel by the preceding stimulus and the following stimulus can not effectively be potentiated which made it impossible to integrate the sequential within-modality stimuli.