|Title:||Feed-forward thalamic modulation and neuroplasticity in the auditory cortex|
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Rehabilitation Sciences|
|Pages:||xiv, 76 p. : ill. ; 30 cm.|
|Abstract:||Auditory signals sensed by the hair cells pass through many relay stages in the auditory pathway. The signals are segregated and modulated at all the relay stages. At the last relay before reaching to the auditory cortex, signals are segregated in the medial geniculate body (MGB) into three divisions: the ventral (MGv), the dorsal (MGd), and the medial (MGm) divisions. We paid attention to the anatomical differences between the MGv and MGm. Firstly, the MGv projects very focally to the primary auditory cortex, while the MGm projects greatly to entire auditory cortex and beyond. Secondly, comparing with the uniformly shaped MGv neurons, neurons in MGm have varied shapes from small to giant. The MGm is also called the magnocellular nucleus. Thirdly, the MGv projects to layers III and IV in the cortex, while the MGm projects to layers I and VI. It is interesting to note that many MGm neurons show the shortest response latency to the auditory stimuli in the MGB. The first question of the present study was what the fast signals from giant cells in the MGm do in the auditory cortex. We hypothesized that the MGm has a feed-forward modulation of the neuronal response to the later coming signals from the MGv in the auditory cortex. As the MGm projects to the superficial layer, we ask the second question: how the superficial layer neurons modulate the neuronal activities in other layers? In the present study, we examined neuronal responses to the auditory stimuli in the auditory cortex of the anaesthetized guinea pig, with combination intracellular and extracellular recordings. The MGm or MGv was reversibly inactivated with local application of lidocaine. The firing mode of cortical neurons in responses to acoustic stimuli was changed after the MGm was reversibly inactivated. However, the inactivation of MGv totally abolished the neuronal responses in the auditory cortex. Each auditory stimulus with the inter-stimulus interval (ISI) of 3s evoked an oscillatory response in the auditory cortex, when the MGm was intact. The same stimulus became less capable in triggering the oscillatory response when the MGm was inactivated. The latency of the onset excitatory post-synaptic potential (EPSP) auditory response increased after the MGm was inactivated. Electrical activation of a small region of the superficial layer neurons of the auditory cortex caused a change in the state of spontaneous neuronal responses from slow oscillatory mode to tonic mode. Activation of single neuron in the superficial layer also caused a change in the state of the spontaneous activities of the activated neuron, the neighboring neurons in different layers with extracellular recording, and even in the field potential in a distant (> 2 mm) electrode. Putting the above results together, we concluded that the fast responding giant MGm neurons placed a strong feed-forward modulatory effect on the auditory cortex through their projection to the superficial layer. The modulation was wide-spread in the auditory cortex and possible beyond the auditory modality.|
In the next part of the study, we focused on the neuronal plasticity in the auditory cortex. The plasticity of synapse is widely accepted as a candidate mechanism of learning and memory in the brain. From the first published long term potentiation (LTP) induction experiment by Tim Bliss and colleagues in 1972, most experimenters have induced LTP through high frequency or repeated stimuli. Such artificial stimulus patterns in the experimental preparation are, however, uncommon in natural condition. The hippocampus is widely believed to serve only as a memory buffer instead of the location to store permanent memory. The cerebral cortex is regarded as the site for long term memory storage. In a parallel study by Chen and colleagues in our laboratory, they have found that an artificial visuoauditory memory trace could be induced in the auditory cortex through conditioning a combined stimulus of electrical stimulation of the auditory cortex and a visual stimulus with foot shock in the behaving rat. The auditory cortex started to respond to the visual stimulus after some 20 trials conditioning. However, the induction was blocked after drug inactivation of the entorhinal cortex of the medial temporal lobe. A further parallel study in our lab has revealed that the projection neurons from the entorhinal cortex to the auditory cortex were cholecystokinin (CCK) neurons and inactivation of the CCK receptors in the auditory cortex blocked the above artificial visuoauditory memory traces in the auditory cortex, similar to the experiment of the inactivation of the entorhinal cortex. We hypothesized that the plasticity in the auditory cortex needed the presence of CCK. In the following study, we first used the in-vivo intracellular recording technique to examine neurons in the auditory cortex to see if they could change their responses to the auditory or visual stimuli after pairing of the conditioned stimulus with depolarization of the recorded neurons. Spikes were triggered by the depolarized current. The EPSP response to the conditioned auditory stimulus was potentiated from 3.9±1.6 to 5.1±1.7 mV at 4 min after the 2-trial pairings of the presynaptic input and postsynaptic firing in the presence of CCK (P<0.01, n=14, paired student t-test). The potentiation lasted as long as the recording was kept from 10min to 110min. No synaptic potentiation was observed (1) after simultaneous co-occurrence of pre- and postsynaptic activities, but without the local application of CCK in the auditory cortex, (2) after only presynaptic activity in the presence of CCK, and (3) after only postsynaptic firings in the presence of CCK. The auditory neurons started to response to the visual stimulus after it was paired with the depolarization for 40 trials (n=2). In the presence of CCK, the neurons in the auditory cortex changed their responses to the conditioned electrical stimulation in the nearby cortex but not to that at the control site, where no conditioning was made. In the following in vitro experiment, we investigated the temporal relationship between the CCK receptor activation and neuronal plasticity postsynaptically. We adopted the patch-clamp technique on cultured cortical neurons of the rat. Pairing of a simultaneous puffing of CCK and glutamate and the depolarization of the neuron did not induce change in the neural response to the glutamate puffing. When the puffing of CCK advanced the puffing of glutamate by 20 to 90s (20, 60, and 90s) in the pairing, potentiation in the EPSP to glutamate puffing was achieved. When the interval between the puffs of CCK and glutamate was further prolonged to 120s, no potentiation was observed. In summary of the second part, neuroplasticity could happen in the auditory cortex of the anaesthetized guinea pig in the presence of CCK. The CCK receptors had to be activated earlier than the pre- and post-synaptic co-activities in 20-90s, in order to produce synaptic plasticity change of neuron.
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