Shorter Trace Interval Research Articles

Long Trace Eyeblink Conditioning Is Largely Preserved in Essential Tremor

The cerebellum and the prefrontal cortex are assumed to play a role in the pathophysiology of essential tremor (ET). Trace eyeblink conditioning with a long interstimulus interval relies on an intact function of the hippocampus, prefrontal cortex (PFC), and, although marginally, of the cerebellum. The aim of the present study was to evaluate whether long trace eyeblink conditioning is impaired in patients with ET. In 18 patients with ET and 18 controls, a long trace conditioning paradigm was applied. Following 100 paired conditioned response-unconditioned response trials, 30 conditioned response alone trials were given as extinction trials. The degree of tremor and the presence of accompanying cerebellar signs were determined based on clinical scales. The acquisition of conditioned eyeblink responses was not impaired in the group of all patients compared to controls (mean total incidences of conditioned responses in patients 23.3 ± 14.5%, in controls 24.1 ± 13.9%; P = 0.88). In the subgroup of six patients with cerebellar signs, incidences of conditioned responses were numerically but not significantly lower (16.4 ± 9.9%) compared to patients without cerebellar signs (26.8 ± 15.5%; P = 0.16). Trace eyeblink conditioning with a long interstimulus interval was not impaired in subjects with ET. Patients with clinical cerebellar signs presented slightly reduced conditioning. Areas of the PFC contributing to trace eyeblink conditioning appear less affected in ET. Future studies also using a shorter trace interval should include a larger group of subjects in all stages of ET.

Changing the rate and hippocampal dependence of trace eyeblink conditioning: Slow learning enhances survival of new neurons

Trace eyeblink conditioning in which a conditioned stimulus and unconditioned stimulus are separated by a gap, is hippocampal dependent and can rescue new neurons in the adult dentate gyrus from death (e.g., Beylin et al., 2001; Gould et al., 1999). Tasks requiring more training trials for reliable expression of the conditioned response are most effective in enhancing survival of neurons ( Waddell & Shors, 2008). To dissociate hippocampal dependence from acquisition rate, we facilitated hippocampal-dependent trace eyeblink conditioning in two ways: a shorter trace interval and signaling the intertrial interval with a post-US cue. Trace conditioning with a shorter trace interval (250 ms) requires an intact hippocampus, and acquisition is faster relative to rats trained with a 500 ms trace interval (e.g., Weiss et al., 1999). Using excitotoxic hippocampal lesions, we confirmed that eyeblink conditioning with the 250 or 500 ms trace interval is hippocampal dependent. However, training with the post-US cue was not hippocampal dependent. The majority of lesion rats in this condition reached criterion of conditioned responding. To determine whether hippocampal dependence is sufficient to rescue adult-generated neurons in the dentate gyrus, rats were injected with BrdU and trained in one of the three trace eyeblink arrangements one week later. Of these training procedures, only the 500 ms trace interval enhanced survival of new cells; acquisition of this task proceeded slowly relative to the 250 ms and post-US cue conditions. These data demonstrate that rate of acquisition and not hippocampal dependence determines the impact of learning on adult neurogenesis.

The Neural Mechanisms Underlying Trace Auditory Fear Conditioning Depends on the Length of the Trace Interval

Event Abstract Back to Event The Neural Mechanisms Underlying Trace Auditory Fear Conditioning Depends on the Length of the Trace Interval Marta Guimarais1*, N. Guyon1 and Marta Moita1 1 Instituto Gulbenkian de Ciencia/ Fundacao Champalimaud, Portugal During trace auditory fear conditioning (tAFC) animals learn to fear a tone that is followed by a footshock. The mechanisms underlying the association between a tone and shock, that occur separate in time, remain elusive. Several studies have shown that the hippocampus is required for the acquisition of the tone-shock association only when the two stimuli are separate in time. Due to its role in spatial and episodic memory, it is possible that the hippocampus contributes to tAFC by linking events, tone and shock, to the spatial context in which they occur. In addition, it has been shown that tAFC requires an intact medial prefrontal cortex (mPFC) raising the possibility that this association could be acquired using working memory, which maintains a memory of the tone until the shock is delivered. We believe that both episodic and working like memory maybe used during tAFC, engaging respectively the hippocampus and the mPFC. Furthermore, as a previous study showed that the hippocampus is involved in the tFC acquisition only when the tone and shock are separated by longer intervals (more than 10 seconds), we hypothesized that the length of the temporal gap between the two stimuli may influence which strategy, working or episodic memory, will predominate in the learning of the tone-sock association. We set out to test this hypothesis, first by confirming this previous finding. We performed pre-training inactivation of the hippocampus in rats using muscimol or PBS as a control. After the infusion all rats where trained with a single tone-shock pairing using either a 5s or a 40s trace interval at the end of which footshock was delivered. We found that hippocampal inactivation disrupted the acquisition of the tone-shock association when 40s, but not 5s, were used as trace interval.According to our hypothesis the animals could employ a different learning strategy during learning of tAFC paradigm depending on the length of the trace interval. As the hippocampus is engaged only when a longer interval is used, and because the mPFC is involved in this form of learning (see above), it is possible that a short interval between tone and shock requires the mPFC because a working memory like strategy is being use to form tone-shock association. Consequently inactivating this structure should impair tAFC learning when a short trace interval (5s) is used. To test this, animals were divided in two groups, one receiving pre-training muscimol infusion and the other PBS as a control. After infusion, both groups were training using a single tAFC tone-shock pairing protocol with a 5s trace interval. As expected, pre-training mPFC muscimol inactivation significantly impairs the learning of tone-shock association in aTFC when using a short trace interval (5s).In conclusion, our results show that the length of the interval between tone and shock determines which structures are required for learning their association. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Citation: Guimarais M, Guyon N and Moita M (2009). The Neural Mechanisms Underlying Trace Auditory Fear Conditioning Depends on the Length of the Trace Interval. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.122 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Aug 2009; Published Online: 11 Aug 2009. * Correspondence: Marta Guimarais, Instituto Gulbenkian de Ciencia/ Fundacao Champalimaud, Oeiras, Portugal, nemoABS01@frontiersin.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marta Guimarais N. Guyon Marta Moita Google Marta Guimarais N. Guyon Marta Moita Google Scholar Marta Guimarais N. Guyon Marta Moita PubMed Marta Guimarais N. Guyon Marta Moita Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals

To elucidate whether the cerebellar cortex may contribute to trace eyeblink conditioning in humans, eight patients with degenerative cerebellar disorders (four with sporadic adult onset ataxia, three with autosomal dominant cerebellar ataxia type III and one with spinocerebellar ataxia type 6) and eight age- and sex-matched healthy control subjects were investigated. Individual high resolution three-dimensional MRI data sets were acquired. As revealed by volumetric measurements of the cerebellum using ECCET software, patients showed cerebellar atrophy to various degrees. No abnormalities were observed in the control subjects. Eyeblink conditioning was performed twice using a tone of 40 ms as conditioned stimulus, followed by a short (400 ms) and a long (1,000 ms) trace interval and an air-puff of 100 ms as unconditioned stimulus. Using the short trace interval, eyeblink conditioning was significantly impaired in cerebellar patients compared to controls, even in those who fulfilled criteria of awareness. Using the long trace interval no significant group differences could be observed. The present findings of impaired trace eyeblink acquisition in patients with cortical cerebellar degeneration suggest that the cerebellar cortex in humans, in addition to the interposed nucleus, is involved in trace eyeblink conditioning, if the trace interval is relatively short. Using a long trace interval, the cerebellum appears to be less important.

Hippocampal activity, but not plasticity, is required for early consolidation of fear conditioning with a short trace interval

The dorsal hippocampus is required for explicit cue fear conditioning only when a temporal gap is inserted between conditioned stimulus (CS) termination and unconditioned stimulus (US) onset (trace fear conditioning). To examine the role of the dorsal hippocampus in associating temporally discontiguous stimuli and to minimize the potential contribution of contextual cues, fear conditioning was conducted using a relatively short (3-s) trace interval. Inactivation of the dorsal hippocampus using the AMPA receptor antagonist NBQX (3 microg/hemisphere) or the GABA(A) agonist muscimol (5 microg/hemisphere) disrupted trace fear conditioning when conducted immediately following training. Trace conditioning was not disrupted significantly when NBQX was infused either before or 2 h after training. Similarly, NBQX infusions were not effective when the CS and US overlapped (delay conditioning). Moreover, trace conditioning was not impaired by intrahippocampal infusion of either the NMDA receptor antagonist AP5 (5 microg/hemisphere) or the L-type voltage-gated calcium channel (VGCC) blocker diltiazem (20 or 40 microg/hemisphere). These data suggest that the involvement of the dorsal hippocampus in short trace interval fear conditioning is largely restricted to the early period of memory consolidation, during which time it mediates the storage of long-term memory in other brain regions.

Characterization of hippocampal theta rhythm in wild-type mice and glutamate receptor subunit δ2 mutant mice during eyeblink conditioning with a short trace interval

We have shown that glutamate receptor subunit δ2 (GluRδ2) null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay eyeblink conditioning but not in trace eyeblink conditioning, even with a 0-trace interval. Such 0-trace conditioning does not depend critically on the hippocampus in wild-type mice, but it does in GluRδ2 mutant mice. Here we examined the hippocampal electroencephalogram (EEG) during 0-trace conditioning in GluRδ2 mutant and wild-type mice. During the apparatus habituation sessions, the total hippocampal theta activity (4–12 Hz) of GluRδ2 mutant mice was less than that of wild-type mice. Activity in the higher frequency band (8–12 Hz, type 1) in GluRδ2 mutant mice was significantly less than it was in wild-type mice, but activity in the lower frequency band (4–8 Hz, type 2) was not. As learning proceeded during the acquisition sessions, the total theta activity decreased in many of the wild-type mice, while this phenomenon was less prominent in GluRδ2 mutant mice. Further analysis showed that the type 1 activity in wild-type mice increased in the early sessions and then decreased, while that in GluRδ2 mutant mice did not change. Type 2 activity tended to decrease in both types of mice as the conditioning proceeded. These results indicate that the distribution of hippocampal EEG frequency and its properties during conditioning are different between wild-type and GluRδ2 mutant mice, suggesting that the cerebellar cortical dysfunction may cause an alteration in the electrophysiological characteristics of the hippocampus.

Hippocampal Damage Disrupts Eyeblink Conditioning in Mice Lacking Glutamate Receptor Subunit δ2.

Cerebellar long-term depression (LTD) at the parallel fiber-Purkinje cell synapses has been proposed to be a neural substrate for classical eyeblink conditioning. Mutant mice lacking the glutamate receptor subunit δ2 (GluRδ2), in which the cerebellar LTD is disrupted, exhibited a severe impairment in the delay eyeblink conditioning with a temporal overlap of CS and US. However, they learned normally trace and delay conditioning without CS-US overlap, suggesting a learning mechanism which does not require the cerebellar LTD.In the present study, we tested possible involvement of the hippocampus in this cerebellar LTD-independent learning. We examined effects of scopolamine and hippocampal lesion on the delay conditioning without CS-US overlap. TheGluRδ2 mutant mice that received scopolamine or aspiration of the dorsalhippocampus together with its overlying cortex exhibited a severe impairment in learning, while the control mutant mice that received saline or aspiration of the overlying cortex learned normally. In contrast, wild-type mice that received either treatment learned as normally as the control wild-type mice. These results suggest that the hippocampus is essential in the cerebellar LTD-independent learning in the GluRδ2 mutant mice, indicating a newrole of hippocampus in the paradigm with a short trace interval.

Enhanced behavioral conditioning to context and impaired behavioral and neuroendocrine responses to conditioned stimuli following ceruleocortical noradrenergic lesions: support for an attentional hypothesis of central noradrenergic function

This study tested the hypothesis that cortical noradrenaline (NA) depletion induced by 6-hydroxydopamine (6-OHDA) widens attentional span, impairing the acquisition of conditioning to an explicit stimulus while enhancing conditioning to contextual stimuli. Sham-operated and NA-depleted rats were exposed to pairings of an auditory (clicker) CS and (footshock) US in a distinctive environment. Half of the lesioned and half of the control animals were trained with a short trace interval between presentations of clicker and shock, and half with a long trace. Associative learning theory predicts that a long trace interval should bias intact animals towards stronger contextual conditioning and, in contrast, a short trace interval should bias controls towards stronger CS conditioning. During testing, NA-depleted animals showed impaired fear conditioning to explicit cues, compared with controls, indicated by their reduced suppression of drinking when the CS was introduced into a separate, lick-operant chamber. In contrast, the same animals exhibited enhanced fear of contextual cues, as shown by their greater preference for a "safe" environment over the one in which they were shocked. The behavioral and plasma corticosterone responses of individual animals to the CS were positively correlated in both the lesion and sham groups. Corticosterone levels corroborated the impairment in CS conditioning caused by the lesion. In contrast, behavioral and corticosterone responses to contextual stimuli were not significantly correlated in either group, and there was no enhancement of the corticosterone response to contextual stimuli in the lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)