scholarly journals Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol

2012 ◽  
Vol 107 (1) ◽  
pp. 273-282 ◽  
Author(s):  
Svitlana Zbarska ◽  
Vlastislav Bracha

The inferior olive (IO) is a major component of the eyeblink conditioning neural network. The cerebellar learning hypothesis assumes that the IO supplies the cerebellum with a “teaching” unconditioned stimulus input required for the acquisition of the conditioned response (CR) and predicts that inactivating this input leads to the extinction of CRs. Previous tests of this prediction attempted to block the teaching input by blocking glutamatergic sensory inputs in the IO. These tests were inconclusive because blocking glutamate neurotransmission in the IO produces a nonspecific tonic malfunction of cerebellar circuits. The purpose of the present experiment was to examine whether the behavioral outcomes of blocking glutamate receptors in the IO could be counterbalanced by reducing GABA-mediated inhibition in the IO. We found that injecting the IO with the glutamate antagonist γ-d-glutamylglycine (DGG) abolished previously learned CRs, whereas injecting the GABAA receptor antagonist gabazine at the same site did not affect CR incidence but shortened CR latencies and produced tonic eyelid closure. To test whether the glutamate antagonist-induced behavioral deficit could be offset by elevating IO activity with GABAA antagonists, rabbits were first injected with DGG and then with gabazine in the same training session. While DGG abolished CRs, follow-up injections of gabazine accelerated their recovery. These findings suggest that the level of IO neuronal activity is critical for the performance of CRs, and that combined pharmacological approaches that maintain spontaneous activity at near normal levels hold tremendous potential for unveiling the role of IO-mediated signals in eyeblink conditioning.

1996 ◽  
Vol 76 (5) ◽  
pp. 3126-3135 ◽  
Author(s):  
N. A. Breakwell ◽  
M. J. Rowan ◽  
R. Anwyl

1. We reexamined the important areas of conflict in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced potentiation of the field excitatory postsynaptic potential (EPSP) and, for the first time, investigated the role of mGluRs in EPSP-spike (E-S) coupling. 2. (1S,3R)-ACPD (10 microM) bath applied for 20 min consistently induced a long-lasting potentiation of the dendritic EPSP in area CA1 of submerged rat hippocampal slices, which was considerably faster in onset than described previously. 3. This effect was not associated with any change in presynaptic fiber volley but was dependent on both an intact CA3 connection, because removal of area CA3 blocked (1S,3R)-ACPD-induced potentiation, and also on functional N-methyl-D-aspartate (NMDA) receptors, because (1S,3R)-ACPD-induced potentiation was blocked by inclusion of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). 4. (1S,3R)-ACPD induced a long-lasting potentiation of the population spike (PS) amplitude that was consistently larger than that of the EPSP measured in the cell body area. This EPSP-PS (E-S) potentiation was blocked by inclusion of the gamma-aminobuturic acid-A (GABAA) receptor antagonist, picrotoxin (50 microM). 5. E-S potentiation induced by high-frequency stimulation (HFS), which was of the same magnitude as that induced by (1S,3R)-ACPD, was blocked by the mGluR-selective antagonist (+)-alpha-methyl-4-carboxyphenylglycine (+MCPG; 250 microM). +MCPG also blocked HFS-induced long-term potentiation (LTP) of the EPSP measured in the cell body. 6. These results suggest that (1S,3R)-ACPD-induced potentiation is NMDA receptor dependent, contrary to some previous findings, and provide further evidence that both synaptic and E-S potentiation induced by (1S,3R)-ACPD share common mechanisms of expression with HFS-induced LTP. The data emphasize the important role of mGluRs in induction of EPSP LTP and E-S potentiation.


1996 ◽  
Vol 317 (2-3) ◽  
pp. 301-307 ◽  
Author(s):  
Tahir Tellioǧlu ◽  
Serap Akin ◽  
Uǧur Özkutlu ◽  
Şule Oktay ◽  
Filiz Onat

Author(s):  
Jodi T Thomas ◽  
Blake L Spady ◽  
Philip L Munday ◽  
Sue-Ann Watson

Projected future carbon dioxide (CO2) levels in the ocean can alter marine animal behaviours. Disrupted functioning of γ-aminobutyric acid type A (GABAA) receptors (ligand-gated chloride channels) is suggested to underlie CO2-induced behavioural changes in fish. However, the mechanisms underlying behavioural changes in marine invertebrates are poorly understood. We pharmacologically tested the role of GABA-, glutamate-, acetylcholine- and dopamine-gated chloride channels in CO2-induced behavioural changes in a cephalopod, the two-toned pygmy squid (Idiosepius pygmaeus). We exposed squid to ambient (∼450 µatm) or elevated (∼1,000 µatm) CO2 for seven days. Squid were treated with sham, the GABAA receptor antagonist gabazine, or the non-specific GABAA receptor antagonist picrotoxin, before measurement of conspecific-directed behaviours and activity levels upon mirror exposure. Elevated CO2 increased conspecific-directed attraction and aggression, as well as activity levels. For some CO2-affected behaviours, both gabazine and picrotoxin had a different effect at elevated compared to ambient CO2, providing robust support for the GABA hypothesis within cephalopods. In another behavioural trait, picrotoxin but not gabazine had a different effect in elevated compared to ambient CO2, providing the first pharmacological evidence, in fish and marine invertebrates, for altered functioning of ligand-gated chloride channels, other than the GABAA R, underlying CO2-induced behavioural changes. For some other behaviours, both gabazine and picrotoxin had a similar effect in elevated and ambient CO2, suggesting altered function of ligand-gated chloride channels was not responsible for these CO2-induced changes. Multiple mechanisms may be involved, which could explain the variability in the CO2 and drug treatment effects across behaviours.


2014 ◽  
Vol 112 (9) ◽  
pp. 2234-2250 ◽  
Author(s):  
Alireza Kashef ◽  
Matthew M. Campolattaro ◽  
John H. Freeman

During delay eyeblink conditioning, rats learn to produce an eyelid-closure conditioned response (CR) to a conditioned stimulus (CS), such as a light, which precedes and coterminates with an unconditioned stimulus (US). Previous studies have suggested that the ventral lateral geniculate nucleus (LGNv) might play an important role in visual eyeblink conditioning by supplying visual sensory input to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No prior study has investigated LGNv neuronal activity during eyeblink conditioning. The present study used multiple tetrodes to monitor single-unit activity in the rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training conditions. This behavioral-training sequence was used to investigate nonassociative- and associative-driven neuronal activity in the LGNv during training. LGNv neuronal activity habituated during unpaired training and then recovered from habituation during subsequent paired training, which may indicate that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal activity correlated with CR production during paired but not unpaired CS/US training. Cerebellar feedback to the LGNv may play a role in modulating LGNv activity and attention to the CS during paired training. Based on the present findings, we hypothesize that the role of LGNv in visual eyeblink conditioning goes beyond simply routing visual CS information to the PN and involves modulation of attention.


2020 ◽  
Author(s):  
Sang-Yoon Kim ◽  
Woochang Lim

We consider the Pavlovian eyeblink conditioning (EBC) via repeated presentation of paired conditioned stimulus (tone) and unconditioned stimulus (airpuff). The influence of various temporal recoding of granule cells on the EBC is investigated in a cerebellar network where the connection probability pc from Golgi to granule cells is changed. In an optimal case of , individual granule cells show various well- and ill-matched firing patterns relative to the unconditioned stimulus. Then, these variously-recoded signals are fed into the Purkinje cells (PCs) through parallel-fibers (PFs), and the instructor climbing-fiber (CF) signals from the inferior olive depress them effectively. In the case of well-matched PF-PC synapses, their synaptic weights are strongly depressed through strong long-term depression (LTD). On the other hand, practically no LTD occurs for the ill-matched PF-PC synapses. This type of “effective” depression at the PF-PC synapses coordinates firings of PCs effectively, which then make effective inhibitory coordination on cerebellar nucleus neuron [which elicits conditioned response (CR; eyeblink)]. When the learning trial passes a threshold, acquisition of CR begins. In this case, the timing degree 𝒯d of CR becomes good due to presence of the ill-matched firing group which plays a role of protection barrier for the timing. With further increase in the trial, strength 𝒮 of CR (corresponding to the amplitude of eyelid closure) increases due to strong LTD in the well-matched firing group, while its timing degree 𝒯d decreases. In this way, the well- and the ill-matched firing groups play their own roles for the strength and the timing of CR, respectively. Thus, with increasing the learning trial, the (overall) learning efficiency degree ℒe (taking into consideration both timing and strength of CR) for the CR is increased, and eventually it becomes saturated. By changing pc from , we also investigate the influence of various temporal recoding on the EBC. It is thus found that, the more various in temporal recoding, the more effective in learning for the Pavlovian EBC.


2021 ◽  
Vol 35 (1) ◽  
pp. 35-42
Author(s):  
José Luis Marcos ◽  
Azahara Marcos

Abstract. The aim of this study was to determine if contingency awareness between the conditioned (CS) and unconditioned stimulus (US) is necessary for concurrent electrodermal and eyeblink conditioning to masked stimuli. An angry woman’s face (CS+) and a fearful face (CS−) were presented for 23 milliseconds (ms) and followed by a neutral face as a mask. A 98 dB noise burst (US) was administered 477 ms after CS+ offset to elicit both electrodermal and eyeblink responses. For the unmasking conditioning a 176 ms blank screen was inserted between the CS and the mask. Contingency awareness was assessed using trial-by-trial ratings of US-expectancy in a post-conditioning phase. The results showed acquisition of differential electrodermal and eyeblink conditioning in aware, but not in unaware participants. Acquisition of differential eyeblink conditioning required more trials than electrodermal conditioning. These results provided strong evidence of the causal role of contingency awareness on differential eyeblink and electrodermal conditioning.


2021 ◽  
pp. 0044118X2199637
Author(s):  
Melissa S. Jones ◽  
Hayley Pierce ◽  
Constance L. Chapple

Though considerable research links both a lack of self-control and adverse childhood experiences (ACEs) to a variety of negative health and behavioral outcomes, few studies to date have explored whether ACEs are associated with deficits in self-control. Using data from the Fragile Families and Child Wellbeing Study (FFCW; n = 3,444) and a life course theoretical framework, this study aims to address this gap in the literature by examining the relationships between individual ACEs, cumulative ACEs, timing of ACEs, and durations of early ACEs and self-control development among youth. Our results indicate that as the number of ACEs (by age 5) experienced incrementally increases, the likelihood of reported self-control decreases. Moreover, when it comes to the timing and duration of ACE exposure, ACEs that are high but late, intermittent, or chronically high significantly decrease self-control. Based on our findings, researchers should continue to explore the role of ACEs in youth self-control development.


Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.


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