Very short-term potentiation of climbing fiber effects on deep cerebellar nuclei neurons by conditioning stimulation of mossy fiber afferents

1994 ◽  
Vol 101 (1) ◽  
Author(s):  
Agn�s Gruart ◽  
Pablo Bl�zquez ◽  
AngelM. Pastor ◽  
Jos�M. Delgado-Garc�a
1991 ◽  
Vol 65 (1) ◽  
pp. 20-32 ◽  
Author(s):  
Y. Komatsu ◽  
S. Nakajima ◽  
K. Toyama

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josef Turecek ◽  
Wade G Regehr

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both. Whether the same boutons, neurons or sources provide these kinetically distinct types of inhibition was not known. We find that in mice the deep cerebellar nuclei (DCN) and vestibular nuclei (VN) are two major sources of inhibition to the IO that are specialized to provide inhibitory input with distinct kinetics. DCN to IO synapses lack fast synaptotagmin isoforms, release neurotransmitter asynchronously, and are exclusively GABAergic. VN to IO synapses contain fast synaptotagmin isoforms, release neurotransmitter synchronously, and are mediated by combined GABAergic and glycinergic transmission. These findings indicate that VN and DCN inhibitory inputs to the IO are suited to control different aspects of IO activity.


1990 ◽  
Vol 64 (1) ◽  
pp. 179-190 ◽  
Author(s):  
M. E. Hasselmo ◽  
J. M. Bower

1. The effects of low-frequency stimulus trains on synaptically evoked responses in piriform cortex pyramidal cells were studied by the use of intracellular recording techniques in an in vitro slice preparation. Afferent and association fiber systems were differentially stimulated with electrodes placed in layer 1a or layer 1b, respectively. To quantify synapse modifiability, the heights of postsynaptic potentials (PSPs) elicited by paired-pulse stimulation (100-ms interval) were averaged over a 50-s period before and after a set of 10 stimulus trains (10 pulses each, 20 Hz, 5-s interpulse interval). 2. Afferent and association fibers showed consistent differences in their response to stimulation during the period lasting from approximately 10 to 200 s after presentation of trains. During this time period, the responses to stimulation of association fibers in layer 1b displayed a short-term potentiation, which over the 10 posttrain trials, produced an average increase in PSP height of 23.2 +/- 3.7% (mean +/- SE). On the other hand, responses to layer 1a stimulation showed an average depression of 10.9 +/- 3.6%. Layer 1b potentiation decayed with time constant roughly estimated at 79 s. Layer 1b potentiation appeared even at very low stimulus voltages and after local association fiber input had been cut, suggesting that it was largely a monosynaptic effect. 3. In the period immediately after train presentations, responses evoked by both layers showed a short-term augmentation with a time constant around 3 s. In layer 1a, this augmentation was superimposed on a depression with slow recovery. At longer times after train presentation (greater than 5 min), 2 cells out of 46 showed changes (increases) in synaptic efficacy in response to layer 1b stimulation. 4. In the current experiments both layers 1a and 1b showed statistically significant facilitation before the presentation of stimulus trains. However, layer 1b facilitation decreased from 22.7 +/- 3.5% to a statistically insignificant 3.9 +/- 3.3% after the presentation of trains, whereas layer 1a facilitation remained at a statistically significant level of 23.1 +/- 5.7%. 5. These experiments show that pyramidal cell responses to stimulation of the afferent and association fiber systems are affected differently by the previous presentation of trains of stimuli. This suggests that mechanisms of synaptic modification may differ between the afferent and intrinsic association synaptic projections onto single pyramidal cells in olfactory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)


1995 ◽  
Vol 74 (6) ◽  
pp. 2573-2589 ◽  
Author(s):  
N. H. Barmack ◽  
H. Shojaku

1. The cerebellar uvula-nodulus receives vestibular projections from primary and secondary vestibular afferents as well as vestibularly related climbing fibers. It also receives visually related information from climbing fiber pathways. In this experiment we investigated how this information is mapped onto the uvula-nodulus. We studied the specificity, dynamics, and topographic distribution of climbing fiber responses (CFRs), simple spike responses, and mossy fiber terminal responses evoked by vestibular and optokinetic stimulation in rabbits anesthetized with alpha-chloralose. 2. Vestibularly evoked CFRs were found in the ventral uvula and nodulus. These responses were evoked during static roll tilt of the rabbit about a longitudinal axis and by sinusoidal oscillation about the longitudinal axis. Purely static responses were attributed to stimulation of the utricular otolith by the linear acceleration of gravity. CFRs that lacked a static component were attributed to activation of the semicircular canals. 3. Using a "null technique" we showed that the canal-sensitive CFRs were caused by stimulation of the anterior or posterior semicircular canals. Of the CFRs classified as canal related, 96% could be attributed to stimulation of the vertical semicircular canals. 4. Increases in CFRs were correlated with decreases in simple spike responses in half the Purkinje cells from which we recorded. These climbing-fiber-induced pauses in simple spikes occurred during spontaneous climbing fiber discharge as well as during climbing fiber discharge evoked by vestibular stimulation. The duration of this pause was inversely proportional to the spontaneous level of simple spikes before the occurrence of a CFR. In the other half of the recorded population of Purkinje cells, vestibularly driven CFRs did not alter the simple spike responses. 5. Vestibularly and visually mediated CFRs were topographically represented on the surface of the uvula-nodulus. CFRs driven by ipsilateral otolithic inputs were distributed over the entire mediolateral surface of the uvula-nodulus. CFRs driven by the ipsilateral posterior semicircular canal were distributed in a sagittal strip approximately 1.5 mm wide, extending laterally from the midline of the nodulus. CFRs driven exclusively by horizontal, posterior-->anterior optokinetic stimulation of the ipsilateral eye were distributed in a sagittal strip approximately 0.5 mm wide located 0.5-1.0 mm from the midline and restricted to the ventral nodulus. CFRs driven by the ipsilateral anterior semicircular canal were found in a sagittal strip approximately 1.0 mm wide extending 1.0-2.0 mm from the midline. 6. The sagittal, topographically arrayed climbing fiber strips effectively map a mediolateral gradient of possible postural responses based on vestibular and optokinetic information.


1992 ◽  
Vol 67 (2) ◽  
pp. 401-410 ◽  
Author(s):  
Y. Komatsu ◽  
M. Iwakiri

1. The induction mechanism of long-term potentiation (LTP) in developing visual cortex was studied by recording intracellular responses from layer III-IV cells in slice preparations of kitten visual cortex at 30-40 days after birth. 2. Strong stimulation of white matter produced a late depolarizing response after an orthodromic action potential. This depolarizing response was abolished by membrane depolarization or hyperpolarization caused by current injection through the recording electrode. In addition, this response was reduced by bath application of a low concentration (100 microM) of Ni2+ without any changes in the rising slope of the excitatory postsynaptic potential (EPSP) or orthodromic action potential. This suggests that this response is mediated by low-threshold Ca2+ channels (LTCs). 3. The involvement of LTCs in the induction of LTP was tested. White matter was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes in EPSPs were tested by low-frequency (0.1 Hz) stimulation of white matter. Conditioning stimulation produced a large N-methyl-D-aspartate (NMDA) receptor-mediated depolarizing response in these cells, which obscured the presence of the late depoliarzation. Therefore the test was conducted in a solution containing an NMDA antagonist 2-amino-5-phosphonovalerate (APV). 4. Weak conditioning stimulation, which evoked no LTC responses, never induced LTP; whereas strong conditioning stimulation, which evoked LTC responses, always induced LTP. Strong conditioning stimulation failed to induce LTP when LTC responses were prevented either by membrane depolarization or hyperpolarization or by a bath application of 100 microM Ni2+. 5. In a solution without APV, the application of Ni2+ also prevented the induction of LTP. 6. When cells were impaled by an electrode containing a Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), LTP was never induced, even though LTC responses were evoked by conditioning stimulation. These results indicate that Ca2+ influx into postsynaptic cells through LTCs induces the LTP. 7. The responses mediated by LTCs, which were evoked by the injection of current pulses into the cells, were maximum at the critical period of visual cortical plasticity, suggesting that LTCs in postsynaptic cells regulate the plastic changes in developing visual cortex.


1983 ◽  
Vol 50 (1) ◽  
pp. 205-219 ◽  
Author(s):  
T. J. Ebner ◽  
Q. X. Yu ◽  
J. R. Bloedel

These experiments were designed to test the hypothesis that climbing fiber inputs evoked by a peripheral stimulus increase the responsiveness of Purkinje cells to mossy fiber inputs. This hypothesis was based on a previous series of observations demonstrating that spontaneous climbing fiber inputs are associated with an accentuation of the Purkinje cell responses to subsequent mossy fiber inputs (10, 12). Furthermore, short-term nonpersistent interactions between climbing and mossy fiber inputs have been an important aspect of many theories of cerebellar function (5, 7, 8, 12, 36). Extracellular unitary recordings were made from Purkinje cells in lobule V of decerebrate, unanesthetized cats. To activate mossy and climbing fiber inputs, the forepaw was passively flexed by a Ling vibrator system. A data analysis was developed to sort the simple spike trials into two groups, based on the presence or absence of complex spikes activated by the stimulus. In addition, during those trials in which complex spikes were activated, the simple spike train was aligned on the occurrence of the complex spike. For each simple spike response to the forepaw input, the average firing rate during the response was compared to background both in those trials in which complex spikes were activated and in those in which they were not. The ratio of the response amplitudes in the histograms constructed from these two groups of trials permitted a quantification of the change in responsiveness when climbing fiber inputs were activated. The results show that both excitatory and inhibitory simple spike responses are accentuated when associated with the activation of a complex spike. Using an arbitrary level of a gain change ratio of 120% as indicating a significant modification, 64% of the response components analyzed increased their amplitude when climbing fiber input was present. Simple spike response components occurring prior to complex spike activation were usually not accentuated, although in a few cells the amplitude of this component of the response increased. In addition, in a small number of cells the occurrence of complex spikes was associated with a new simple spike component. For excitatory responses, the magnitude of the gain change ratio was shown to be inversely related to the amplitude of the simple spike response evoked by the mossy fiber inputs. The data obtained is consistent with the hypothesis that the climbing fiber input is associated with an increase in the responsiveness of Purkinje cells to mossy fiber inputs. The increased responsiveness occurs whether the simple spike modulation evoked by the peripheral stimulus is excitatory or inhibitory. The change in responsiveness is short term and nonpersistent. It is argued that the activation of climbing fiber inputs to the cerebellar cortex is associated with an increase in the gain of Purkinje cells to mossy fiber inputs activated by natural peripheral stimuli.


1996 ◽  
Vol 75 (2) ◽  
pp. 894-901 ◽  
Author(s):  
D. Mouginot ◽  
B. H. Gahwiler

1. Recording from deep cerebellar nuclei neurons, we investigated the role of presynaptic gamma-aminobutyric acid-B (GABAB) receptors in the modulation of monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of Purkinje cells in rat slice cultures. 2. Bath application of the GABAB receptor agonist, baclofen (10 and 100 microM) induced two effects in cerebellar nuclei neurons: a postsynaptic hyperpolarization of 4.2 +/- 1.7 (SD) mV and a reduction in the amplitude of evoked IPSPs (30 +/- 10%). 3. When the postsynaptic GABAB response was blocked by filling the electrode with cesium methanesulfonate (2 M), or with a solution containing QX 314 (50 mM), bath application of baclofen (10 microM) reversibly depressed the evoked IPSPs by 36.7 +/- 18.7% and 42 +/- 20.3%, respectively. Under these experimental conditions, baclofen (10 microM) also reduced the amplitude of spontaneous IPSPs (10.2 +/- 9.5%) and decreased their frequency by 45.6 +/- 8.8%, suggesting a presynaptic site of action. 4. The presynaptic action of baclofen was not due to activation of receptors on the somata of Purkinje cells: baclofen (100 microM) failed to alter membrane holding current in Purkinje cells, and it had no effect on the rate of spontaneous action-potential discharge in Purkinje cells in the presence of ionotropic glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; D-2-amino-5-phosphonovalerate, 40 microM). 5. IPSPs could be evoked by extracellular stimulation of the Purkinje cell layer or by direct stimulation of the fiber bundle connecting Purkinje cells to deep cerebellar neurons. In both situations, baclofen (10 microM) reduced the amplitude of evoked IPSPs by 32.7 +/- 8.8% and 31.2 +/- 10.2%, respectively. 6. These results demonstrate that GABAB receptors are present on the terminals of Purkinje cells. Their activation causes a decrease in the amplitude of evoked IPSPs recorded in deep cerebellar nuclei and also reduces the frequency of spontaneous inhibitory events.


2020 ◽  
Author(s):  
E. A. Tsvetkov ◽  
◽  
E. I. Krasnoshchekova ◽  

The monograph provides a review of the world’s published scientific literature on the physiology of emotions that are based on the conditioned reflex reaction of fear. A detailed description of electrophysiological, molecular mechanisms of synaptic plasticity of the amygdala complex (amygdala), and their ability for long-term potentiation (LTP), as the basis for emotions and conditioned memory, is presented in this work. There are two categories of fear: innate and learned. Innate fear is realized like an unconditioned reflex by the genetically determined pathways. Learned fear is realized like a conditioned reflex and is formed as a result of learning during the combination of conditioned and unconditioned signals. A convergence of sensory inputs that carry the information on such signals occurs on the neurons of the lateral nuclei of the amygdala. Two types of amygdala cells (glutamatergic projection and GABAergic interneurons) receive inputs from the thalamus and cortex. The synapses of the projection cells are equally effective, while the thalamic synapses of interneurons are more effective. The response of projection neurons to the stimulation of cortical and thalamic afferents includes the monosynaptic excitatory glutamatergic AMPA and NMDA components and disynaptic inhibitory GABAergic components. The most important resources of the regulation of the excitatory efferents of the amygdala are GABAergic interneurons. During the stimulation of the thalamic input, the synapses of the interneurons shunt the membrane of the projection cells more effectively and decrease the level of long-term potentiation in comparison with the stimulation of the cortical input. The stages of the development of long-term potentiation are similar for short-term and long-term memory. The formation of the conditioned reflex is based on a short-term memory on the coincidence of the conditioned signal with an unconditioned traumatizing stimulus, and the consolidation — on the long-term memory. The association of the conditioned reflex reactions and long-term potentiation verify the results of the experiments on the manipulations with genes that encode proteins regulating the synaptic transmission and its plasticity. In animals with a knocked-out gene of gastrin-releasing peptide, easier initiation of long-term potentiation and formation of conditioned reflex reactions of fear are observed. The knock-out of the gene of oncoprotein18/stathmin leads to a deficit of long-term potentiation and complicates the expression of amygdala-dependent conditioned reflexes. The review and analysis of modern publications and the author’s research supplement the Cannon-Bard theory of emotion with evidence that a key role in the regulation of emotions is played by the amygdala complex that is characterized by neuronal mechanisms of stimuli filtration depending on their relevance, education, and formation of stimulus-conditioned memory. The annexes to the article contain the protocols of the electrophysiological experiments and methods of formation of conditioned reflex reaction of fear in animals.


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