Brainstem Cholinergic Modulation of Muscle Tone in Infant Rats

In week-old rats, lesions of the dorsolateral pontine tegmentum (DLPT) and nucleus pontis oralis (PnO) have opposing effects on nuchal muscle tone. Specifically, pups with DLPT lesions exhibit prolonged bouts of nuchal muscle atonia (indicative of sleep) and pups with PnO lesions exhibit prolonged bouts of high nuchal muscle tone (indicative of wakefulness). Here we test the hypothesis that nuchal muscle tone is modulated, at least in part, by cholinergically mediated interactions between these two regions. First, in unanesthetized pups, we found that chemical infusion of the cholinergic agonist carbachol (22 mM, 0.1 µL) within the DLPT produced high muscle tone. Next, chemical lesions of the nucleus pontis oralis (PnO) were used to produce a chronic state of high nuchal muscle tone, at which time the cholinergic antagonist scopolamine (10 mM, 0.1 µL) was infused into the DLPT. Scopolamine effectively decreased nuchal muscle tone, thus suggesting that lesions of the PnO increase muscle tone via cholinergic activation of the DLPT. Using 2-deoxyglucose (2-DG) autoradiography, metabolic activation throughout the DLPT was observed after PnO lesions. Finally, consistent with the hypothesis that PnO inactivation produces high muscle tone, infusion of the sodium channel blocker, lidocaine (2%), into the PnO of unanesthetized pups produced rapid increases in muscle tone. We conclude that, even early in infancy, the DLPT is critically involved in the regulation of muscle tone and behavioral state and that its activity is modulated by a cholinergic mechanism that is directly or indirectly controlled by the PnO

Neural substrates of avoidance behavior: The afferent limb

During avoidance conditioning, the rabbit sitting in a large activity wheel was presented with two tones. One tone the positive conditional stimulus (CS+), predicted a mild foot-shock, the other tone (CS$-$) did not. The rabbit could learn to avoid the footshock by locomoting in the running wheel. Using a neuronal circuit model of discriminative active avoidance conditioning, sources of afferent input to critical learning-related limbic structures were examined for their influence on neuronal activity and behavior.The current experiments were designed to answer whether the amygdala and the medial geniculate nucleus (MGN) provide critical input to the limbic system for learning the avoidance behavior. In Experiment 1, electrolytic and ibotenic acid lesions of the medial geniculate nucleus severely impaired learning of the avoidance behavior. Additionally, all training-induced activity (TIA) was blocked in the limbic thalamus and cingulate cortex indicating that the MGN afferent input is critical for the development of TIA.Experiment 2 concerned the effects of temporary inactivation of the amygdala at different times during acquisition and maintenance of the avoidance behavior.Temporary inactivation of the amygdala on the first day of training blocked acquisition of the avoidance behavior and development of TIA in the neurons of medial division of the MGN (mMGN) and anterior ventral (AV) thalamic nucleus. On the second day of training, when the amygdala was not inactivated, there were no indications of retention for the first day's learning experience. Performance of the avoidance behavior was impaired after three sessions of overtraining and TIA was decreased in the AV thalamic neurons and increased in the mMGN and medial dorsal (MD) thalamic neurons. However, after an additional seven sessions of overtraining or seven days of rest there were no significant impairment of the avoidance behavior and no changes in TIA. Temporary inactivation of the amygdala on the first training day had long reaching consequences and blocked the normal development of TIA in all of the structures recorded from (except MD thalamic nucleus), and significantly reduced conditioned response performance during the session of criterion.These findings indicate that the MGN and the amygdala are both critical links in the afferent pathway important for the acquisition of the avoidance behavior.U of I OnlyETDs are only available to UIUC Users without author permissio

Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56199/1/marenBRES91.pd

Experiment 1: Mean (± SEM) short-term memory accuracy among sensory modalities for simple, artificial stimuli.

<p>Short-term retention of auditory stimuli declines at a greater rate than retention of visual or tactile stimuli. There were no differences in accuracy among the sensory modalities for trials with brief retention intervals (1–4 s), indicating that the initial discriminability of the stimuli was approximately equal. However, at longer retention intervals (8–32 s), accuracy for auditory trials was significantly lower than visual and tactile trials. Post-hoc tests (<i>p</i><.05, Bonferroni correction for multiple comparisons): *Accuracy in the auditory block significantly lower than the tactile block. †Accuracy in the auditory block significantly lower than the visual block.</p

Comparison of visual and auditory short-term memory among primates.

<p>(A) In the present experiment, inferior retention was observed for auditory compared to visual stimuli in human subjects. This pattern of results is qualitatively similar to that which has been observed in the chimpanzee (B), as well as both old-world (C) and new-world monkeys (D). (B) Adapted from Hashiya and Kojima <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089914#pone.0089914-Hashiya1" target="_blank">[12]</a>; (C) adapted from Fritz et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089914#pone.0089914-Fritz1" target="_blank">[6]</a>; (D) adapted from Colombo and D’Amato <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089914#pone.0089914-Colombo1" target="_blank">[1]</a>.</p

Experiment 2: Mean (+ SEM) recognition accuracy among sensory modalities for complex, naturalistic stimuli.

<p>(A) When tested immediately after the study phase, recognition accuracy was lower for auditory stimuli than visual or tactile stimuli. (B) Similarly, recognition was lower for auditory stimuli when tested 24 hours after the study phase. (C) When tested one week after the study phase, recognition accuracy was significantly lower for auditory stimuli than tactile stimuli, but the difference between auditory and visual recognition was not significant. Post-hoc tests (<i>p</i><.05; Bonferroni correction): *Accuracy in the auditory block significantly lower than the tactile block. †Accuracy in the auditory block significantly lower than the visual block.</p

Achilles’ Ear? Inferior Human Short-Term and Recognition Memory in the Auditory Modality

<div><p>Studies of the memory capabilities of nonhuman primates have consistently revealed a relative weakness for auditory compared to visual or tactile stimuli: extensive training is required to learn auditory memory tasks, and subjects are only capable of retaining acoustic information for a brief period of time. Whether a parallel deficit exists in human auditory memory remains an outstanding question. In the current study, a short-term memory paradigm was used to test human subjects’ retention of simple auditory, visual, and tactile stimuli that were carefully equated in terms of discriminability, stimulus exposure time, and temporal dynamics. Mean accuracy did not differ significantly among sensory modalities at very short retention intervals (1–4 s). However, at longer retention intervals (8–32 s), accuracy for auditory stimuli fell substantially below that observed for visual and tactile stimuli. In the interest of extending the ecological validity of these findings, a second experiment tested recognition memory for complex, naturalistic stimuli that would likely be encountered in everyday life. Subjects were able to identify all stimuli when retention was not required, however, recognition accuracy following a delay period was again inferior for auditory compared to visual and tactile stimuli. Thus, the outcomes of both experiments provide a human parallel to the pattern of results observed in nonhuman primates. The results are interpreted in light of neuropsychological data from nonhuman primates, which suggest a difference in the degree to which auditory, visual, and tactile memory are mediated by the perirhinal and entorhinal cortices.</p></div

Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or muscimol infusions into the MATN contralateral to the trained eye before each of four conditioning sessions with an auditory CS. Rats were then given four additional sessions without infusions to assess savings from the initial training. All rats were then given a retention test with a muscimol infusion followed by a recovery session. Muscimol infusions through cannula placements within 0.5 mm of the MGm prevented acquisition of eyeblink conditioned responses (CRs) and also blocked CR retention. Cannula placements more than 0.5 mm from the MATN did not completely block CR acquisition and had a partial effect on CR retention. The primary and secondary effects of MATN inactivation were examined with 2-deoxy-glucose (2-DG) autoradiography. Differences in 2-DG uptake in the auditory thalamus were consistent with the cannula placements and behavioral results. Differences in 2-DG uptake were found between groups in the ipsilateral auditory cortex, basilar pontine nuclei, and inferior colliculus. Results from this experiment indicate that the MATN contralateral to the trained eye and its projection to the pontine nuclei are necessary for acquisition and retention of eyeblink CRs to an auditory CS