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BACKGROUND AND AIMS: Thalamic relay cells constitute important node of reciprocal sensory processing which is highly dependent on current behavioral demands realized by brainstem neuromodulatory systems. In these experiments, performed on rats’ thalamic brain slices, we have investigated cholinergic influence on synaptic transmission from cortical layer 6 to the posteromedial thalamic nucleus (PoM). METHODS: Neuronal membrane potentials and currents were recorded with whole-cell patch-clamp method and general cholinergic agonist carbachol was added to the bath in order to mimic cholinergic activation. Excitatory postsynaptic responses were evoked in PoM cells by repetitive trains of 5 electrical stimuli delivered at 20 Hz through bipolar electrode placed at the corticothalamic fibers in the internal capsule. RESULTS: In all investigated cells, consecutive postsynaptic responses in the train showed pronounced frequency facilitation (i.e. increase in amplitude). Carbachol substantially decreased postsynaptic response amplitudes, but at the same time it enhanced the magnitude of frequency facilitation. Moreover, the amplitudes of each consecutive postsynaptic potential in the train were characterized by much higher trial-to-trial coefficient of variation (SD/ mean). These effects suggested presynaptic action of carbachol. To prove this, we measured the failure rate of excitatory postsynaptic currents in PoM cells in response to minimum stimulation of corticothalamic fibers. CONCLUSION: The substantial increase of failure rate in the presence of carbachol supports the hypothesis that observed effects of cholinergic modulation relay on decreased probability of transmitter release from presynaptic site. This research and SN were supported by the European Union Regional Development Fund through the Foundation for Polish Science within the frames of International PhD Program in Neurobiology.
Higher order posteromedial thalamic nucleus of the rat (PoM) receives cholinergic (Ach) and noradrenergic (NA) neuromodulatory projections originating from the brain stem. With a whole-cell patch-clamp method we investigated influence of these neuromodulators on membrane potential of PoM neurons in the thalamic slices. Ach (carbachol) or NA (norepinephrine) agonists were added to the bath to mimic the activation of appropriate neuromodulatory system. Both agonists induced slow depolarization of membrane potential by about 9 mV. However, carbachol but not norepinephrine substantially enhanced amplitude of membrane potential fluctuations in the frequency range from 8 to 500 Hz (reaching more than two-fold elevation between 25–180 Hz). These carbachol induced fluctuations were not blocked neither by manual membrane repolarization to the control level, nor by the blockage of GABA-A receptors. Our results suggest that this increase of fluctuation strength might result mainly from activation of muscarinic receptors. This research and SN were supported by the European Union Regional Development Fund through the Foundation for Polish Science within the frames of International PhD Program in Neurobiology.
The second order somatosensory thalamic nucleus (posteromedial nucleus, PoM) receives excitatory projection from layer VI of somatosensory cortex. While it is known that layer VI cortical input to first order, ventrobasal nucleus (VB) is modulated by cholinergic projections from the brainstem, no such data exists concerning the PoM nucleus. In order to study if layer VI corticothalamic transmission to PoM is also modulated we used patch-clamp recording in thalamocortical slices from the rat's brain. Excitatory postsynaptic potentials (EPSPs) were evoked in PoM cells by trains of 5 electrical pulses at 20 Hz frequency applied to corticothalamic fibers. After carbachol was applied to mimic activation of the cholinergic neuromodulatory system corticothalamic EPSP amplitudes were reduced, while facilitation of EPSP amplitudes was enhanced for each next pulse in the series. Such cholinergic control of layer VI corticothalamic synapses in PoM may be used as gain modulator for the transfer of the peripheral sensory information to the cortex.
We have previously shown that cholinergic agonist carbachol modulates synaptic transmission of layer 6 corticothalamic input to posteromedial nucleus of the thalamus. In rat brain slices application of carbachol depresses synaptic responses to stimulation of corticothalamic fibers but enhances their frequency facilitation. Here we show that carbachol acts via activation of muscarinic receptors, because application of muscarinic antagonist (scopolamine or atropine) abolished both: depression of corticothalamic EPSPs and increase of frequency facilitation. In contrary, high concentration (100 µM) of specific nicotinic agonist DMPP (dimethylphenylpiperazinium) neither depressed corticothalamic responses nor enhanced the frequency facilitation. Surprisingly, low concentration of DMPP (10 µM) increased corticothalamic EPSPs, but did not change the frequency facilitation of corticothalamic transmission. This research and SN were supported by the European Union Regional Development Fund through the Foundation for Polish Science within the frames of International PhD Program in Neurobiology
Besides sensory input from whiskers, higher order posteromedial nucleus (PoM) of the thalamus, receives rich and complex cortical feedback projections of modulatory and driving type (from layer 6 and 5, respectively). The function of these recurrent pathways is under control of the brain stem neuromodulatory systems. In this study we investigated cholinergic influence on facilitatory properties of cortical layer 6 input to PoM cells. For this purpose we prepared “classical” thalamocortical slices from brains of young (21-28 days) rats. Such slices are suitable for studying the physiology of synapses made on PoM cells by axons from cortical layer 6, because fibers descending from layer 5 are mostly cut off. Membrane potential of PoM neurons was recorded by whole-cell patch-clamp method while cholinergic agonist carbachol (5-8 µM) was added to the bath to activate cholinergic receptors. To evoke excitatory postsynaptic potentials (EPSPs), repetitive series of 5 electrical stimuli at 20 Hz frequency (15 s inter-trial interval, baseline membrane voltage at -56 mV) were applied by stimulation electrode placed at the cortico-thalamic fiber tract in the internal capsule. Bicuculline was present in the bath to block GABAA receptors. We found that carbachol led to almost threefold decrease of the first EPSP’s amplitude in the train. At the same time, however, the ratio between the second and the first postsynaptic potential (paired pulse facilitation) became nearly two times bigger. Moreover, with activated cholinergic receptors, the following EPSPs in the train also grew faster in amplitude. Our results indicate that modulatory cholinergic system may increase the frequency potentiation of cortical layer 6 input to PoM, most likely due to decrease of transmitter release through activation of presynaptic cholinergic receptors. This research and NS was supported by the Foundation for Polish Science through International PhD Program in Neurobiology.
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