Scopolamine disruption of behavioral and hippocampal responses in appetitive trace classical conditioning

Twelve young rabbits (3–6 months; Oryctolagus cuniculus) were classically conditioned in a trace jaw movement paradigm (300 ms tone, 450 ms trace, 200 ms intraoral water) after implantation of electrodes into area CA1 of dorsal hippocampus. Rabbits were divided into two groups and administered either 0.5 mg/kg scopolamine hydrobromide (HBr) or 0.5 mg/kg scopolamine methylbromide (MBr) subcutaneously before daily training sessions. Rabbits given HBr took significantly more trials to reach a behavioral criterion of eight conditioned responses in any nine consecutive trials than rabbits given MBr (P=0.03). Conditioned, but not unconditioned, rhythmic jaw movement responses of the HBr group were of a lower frequency (Hz) than those of MBr rabbits (P=0.02). The magnitude of hippocampal conditioning-related responses across the first 3 days of training was significantly smaller for HBr rabbits than for MBr rabbits (P=0.02). These effects of central cholinergic blockade are similar to those reported for undrugged aging rabbits trained in the same paradigm (Seager MA, Borgnis RL, Berry SD. Neurobiol. Aging 1997;18(6):631–639).     

Head movements and neck muscle activities associated with the jaw movement during mastication in the rabbit authors

Rhythmical head movements and neck muscle activities associated with the masticatory jaw movement were investigated in rabbits. In natural mastication, head movements and neck muscle activities showed a rhythmical feature synchronized with jaw movement. During cortically induced rhythmical jaw movements, some neck muscle showed rhythmical activity induced by biting a wooden stick. Neck muscles may contribute to the rhythmical head movement after loading the tooth with food.     

Mechanomyographic activity in the human lateral pterygoid muscle during mandibular movement

The activity of the lateral pterygoid muscle has been regarded to be related to the pathological condition of the temporomandibular joint (TMJ) in the craniomandibular disorders. Because the lateral pterygoid muscle is a deep muscle, a needle electrode is necessary for EMG recordings. The purpose of this study was to establish a non-invasive method for the evaluation of muscle activity of the lateral pterygoid muscle using mechanomyogram (MMG). In three male subjects, surface electromyogram (EMG) in the left masseter muscle, left anterior and posterior belly of the temporal muscle, left anterior belly of the digastric muscle and needle EMG of the inferior head of the lateral pterygoid were recorded during mandibular movement tasks simultaneously with the MMG derived from a condenser microphone in the external ear canal. There were significant positive correlations between the needle EMG signal of the lateral pterygoid muscle and the MMG signal for the tasks of static jaw opened position of 30 mm of interincisal distance (p = 0.000, R² = 0.725), static jaw opened position of 40 mm of interincisal distance (p = 0.000, R² = 0.753), 5 mm protruded mandibular position (p = 0.000, R² = 0.653), the most protruded mandibular position (p = 0.000, R² = 0803). On the contrary, for the task of maximal clenching, there was no significant correlation between the EMG signal of the lateral pterygoid muscle and the MMG signal. These results suggest that the activity of the lateral pterygoid muscle could be evaluated by the MMG signals recorded in the external ear canal, unless jaw closing major muscles show active contraction.     

Convergence of selected inputs from sensory afferents to trigeminal premotor neurons with possible projections to masseter motoneurons in the rabbit

Peripheral input convergence on trigeminal premotor neurons in the vicinity of trigeminal motor nucleus has been investigated. Thirty neurons were identified by their antidromic responses to microstimulation of the masseteric subnucleus of trigeminal motor nucleus (NVmot-mass). Peripheral receptive fields were found in the buccal mucosae, periodontal ligaments, palate, tongue and vibrissae for 16 neurons located in the intertrigeminal area (NVint), supratrigeminal area (NVs), main sensory trigeminal nucleus (NVsnpr) and subnucleus gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma). Eleven neurons in the NVint, NVs and NVspo-gamma responded to passive jaw opening: nine neurons were activated and two were inhibited. None of the neurons responded to both the orofacial mechanical stimulation and passive jaw opening. Forty-six percent of neurons (13 out of 28 tested) received inputs from the inferior alveolar nerve (IAN) and 53% of neurons (8 out of 15 tested) received inputs from the infraorbital nerve (ION). Out of 15 neurons tested for inputs from the IAN and ION, 7 neurons in the NVsnpr and NVspo-gamma received input from both. Sixteen percent of neurons (4 out of 25) received inputs from the masseteric nerve (MassN). None of the neurons with inputs from IAN and/or ION also received inputs from the MassN. We suggest that trigeminal premotor interneurons with projections to the NVmot-mass fall into two broad categories, those with inputs from the IAN and/or ION and those with inputs from the MassN, possibly muscle spindle afferents, and no neuron receiving inputs from both.     

Characterization of the neuronal changes in the medial prefrontal cortex during jaw movement and eyeblink Pavlovian conditioning in the rabbit

Medial prefrontal (mPFC) single-unit activity was assessed in defensive (eyeblink, EB) and appetitive (jaw movement, JM) Pavlovian conditioning in the rabbit. Concomitant heart rate (HR) changes were also assessed. In a first experiment robust JM conditioned responses (CRs) were observed to a tone-water (CS+) contingency but not to tone-alone (CS-), indicating discriminative JM conditioning. However, the CS-evoked accelerative HR response was not discriminative. Nevertheless, several single-unit discharge patterns were evoked by both tone-water and tone-alone, many of which were uniquely associated with either the CS+ or CS-. In a second experiment, Three separate stimuli, consisting of tone followed by periorbital shock (tone-shock), water (tone-water), and white noise not followed by shock or water, were presented in the same paradigm. Discrimination of conditioned JM, EB and HR changes were observed, i.e. each of these behavioral responses were uniquely associated with the relevant CS presentation. Conditioned bradycardia was evoked by tone-water during the first training session, which changed to tachycardia with further training. However, conditioned bradycardia was evoked by tone-shock throughout training. Different subpopulations of mPFC cells were activated by the tone-shock and tone-water contingencies, but a small group of cells were activated by both.     

An in vivo model for investigating bilateral synaptic plasticity across CA3/CA1 synapses in guinea pig dorsal hippocampus

A method is described for concurrent investigation of long-term potentiation (LTP) in the left and right CA1 synapses in dorsal hippocampi in guinea pig in vivo. Briefly, animals are anesthetized with urethane, and small access holes are made in the skull through which electrodes are lowered to stimulate the left CA3 and record from both CA1 regions. Using this animal model, we have found that LTP is produced in both CA1 regions, following conditioning stimulation to the left CA3. However, in some animals LTP occurred in the left CA1 without concomitant synaptic potentiation in the contralateral CA1. We also observed that in some experiments synaptic potentiation in the contralateral CA1, when present, decayed to baseline levels even though LTP persisted in the ipsilateral CA1. To conclude, our data on bilateral LTP demonstrates findings that are best addressed in vivo.     

AHP reductions in rabbit hippocampal neurons during conditioning correlate with acquisition of the learned response

Young adult male albino rabbits were conditioned using a free field auditory conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US) in a short delay eye blink paradigm. All rabbits received two 80-trial training sessions. Intracellular recordings were made from hippocampal CA1 pyramidal neurons within brain slices prepared 24 h following the second training session. All 46 CA1 neurons included in the analysis had stable penetration, at least 70 mV impulse amplitudes and at least 40 M omega input resistance. Recording and initial data analysis were done 'blind' regarding behavioral training performance of the rabbit from which the slices were prepared. The animals were separated into a High (86 +/- 6% CRs, n = 12), and Low (12 +/- 4% CRs, n = 10) Acquisition group based on the number of blink CRs shown on the second training day (P less than 0.001). CA1 pyramidal neurons from the High Acquisition group (n = 20) showed a significant reduction in the afterhypolarization (AHP) response following 4 impulses elicited by intracellular current injection as compared to neurons from the Low Acquisition group (n = 26). The mean maximal AHP amplitudes after 4 spikes were -2.9 +/- 0.34 mV and -4.0 +/- 0.31 mV, respectively, in the High and Low Acquisition groups (P less than 0.01). The size of the AHP examined at 100 ms intervals during the first 1.7 s after the current pulse proved to be reduced in the High group both when evaluated for all points (F = 5.88, df = 1.44, P less than 0.02) and for each of the individual time points (at least P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy

It has been hypothesized on the basis of animal models of epilepsy that abnormal neural activity in epilepsy may be related to reorganized neural circuits that facilitate epileptogenesis. Little evidence of this was available for human epilepsy. This paper provides the first evidence of such reorganization of a hippocampal seizure focus in human temporal lobe epilepsy (TLE). This reorganization involves the selective loss of somatostatin and neuropeptide Y immunoreactive interneurons, and axonal sprouting of other neuropeptide Y neurons and dynorphin-A immunoreactive granule cells. This set of changes is not exactly like those that are reported in animal models.     

Angiotensin II-induced rhythmic jaw movements in the ketamine-anesthetized guinea pig

The EMG activity of the left anterior digastric muscle as well as associated jaw movements were studied in ketamine-anesthetized guinea pigs that had received i.v. infusions of angiotensin II (ANG-II). Rhythmic jaw movements with two distinct movement profiles were associated with ANG-II infusion. One movement profile was typified by vertical jaw opening and closing movements with little or no associated horizontal movement. The second rhythmical jaw movement profile was unlike the first in that jaw closing was accompanied by a significant horizontal deflection of the jaw. Both jaw movement profiles were similar in that little or no horizontal movement occurred during jaw opening. Tongue protrusions were also observed during jaw opening in both cases. The results show that ANG-II induces rhythmic jaw movements in anesthetized guinea pigs. ANG-II-induced jaw movement profiles and digastric muscle EMG activity are similar to those seen after an i.v. injection of apomorphine in the anesthetized guinea pig, and to those associated with lapping in the awake animal.     

Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig

To determine if classical conditioning produces general or specific modification of responses to acoustic conditioned stimuli (CS), frequency receptive fields (RF) of neurons in guinea pig auditory cortex were determined before and up to 24 h after fear conditioning. Highly specific RF plasticity characterized by maximal increased responses to the CS frequency and decreased responses to the pretraining best frequency (BF) and other frequencies was observed in 70% of conditioning cases. These opposing changes were often sufficient to produce a shift in tuning such that the frequency of the CS became the new BF. CS frequency specific plasticity was maintained as long as 24 h. Sensitization training produced general increased responses across the RF without CS specificity. The findings indicate that associative processes produce systematic modification of the auditory system's processing of frequency information and exemplify the advantages of combining receptive field analysis with behavioral training in the study of the neural bases of learning and memory.     

Hippocampal neuronal responses during signaled licking of gustatory stimuli in different contexts

Neuroanatomical studies suggest that hippocampal formation (HF) receives information from all sensory modalities including taste via the parahippocampal cortices. To date, however, no neurophysiological study has reported that HF neurons encode taste information. In the present study, we recorded CA1 HF neurons from freely behaving rats during performance of a visually‐guided licking task in two different triangular chambers. When a cue lamp came on, the rats were required to press a bar to trigger a tube to protrude into the chambers for 3 s. During this period, the rats could lick one of six sapid solutions: [0.1M NaCl (salty), 0.3M sucrose (sweet), 0.01M citric acid (sour), 0.0001M quinine HCl (bitter), 0.01M monosodium L ‐glutamate (MSG, umami), and a mixture of MSG and 0.001M disodium‐5′‐inosinate (IMP) (MSG+IMP)], and distilled water. Of a total 285 pyramidal and interneurons, the activity of 173 was correlated with at least one of the events in the task—illumination of cue lamps, bar pressing, or licking the solution. Of these, 137 neurons responded during licking, and responses of 62 of these cells were greater to sapid solutions than to water (taste neurons). Multivariate analyses of the taste neurons suggested that, in the HF, taste quality might be encoded based on hedonic value. Furthermore, the activity of most taste neurons was chamber‐specific. These results implicate the HF in guiding appetitive behaviors such as conditioned place preference. © 2010 Wiley‐Liss, Inc.     

Hippocampal neuronal damage after transient forebrain ischemia in monkeys

To investigate cerebral injury in the monkey due to transient ischemia, monkeys were each subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral) major arteries. After 0 (control), 5, 10, 13, 15, and 18 min occlusion, blood flow was restored. The monkeys were sacrificed by perfusion fixation 5 days after the operation, and all brain regions were then histologically examined for ischemic neuronal changes induced by the occlusion. The amplitude of EEG signals from skull and scalp became almost isoelectric within 1-6 min after the onset of occlusion. The EEG signals from the hippocampus were markedly attenuated within 1-4 min, although they did not become completely isoelectric. Blood pressure was significantly increased after 10-min ischemia. Five-min occlusion produced no ischemic neuronal changes except a slight increment of glial cells in the striatum and III, V, and VI layers of the neocortices. After 10- to 15-min occlusion, there were ischemic cell changes restricted exclusively to the CA1 subfield of the hippocampus. Eighteen-min occlusion produced more prominent ischemic neuronal damage in the CA1 subfield of the hippocampus, but ischemic neuronal damage was no longer confined to the hippocampus. These results suggest that only the CA1 subfield of the monkey hippocampus could be damaged by mild ischemic insult. We demonstrate that the limited lesion of the hippocampus, especially the CA1 subfield, after 10- to 15-min occlusion of eight arteries in the monkey, produces a model equivalent to human amnesia caused by transient ischemic insult.     

Hyperexcitability of the CA1 Hippocampal Region during Epileptogenesis

Summary:  Temporal Lobe Epilepsy (TLE) is often preceded by a latent (seizure-free) period during which complex network reorganizations occur. In experimental epilepsy, network hyperexcitability is already present during the latent period, suggesting a modification of information processing. The purpose of this study was to assess the input/output relationship in the hippocampal CA1 region during epileptogenesis. Field recordings in strata pyramidale and radiatum were used to measure the output of CA1 pyramidal cells as a function of the synaptic inputs they receive following the stimulation of Shaffer collaterals in slices obtained from sham and pilocarpine-treated animals during the latent and chronic periods. We show that there is a transient increase of the input and output field responses during the latent period as compared to sham and epileptic animals. The coupling between excitatory inputs and cell firing was also increased during the latent period. This increase persisted in epileptic animals, although to a lesser extent. We also confirm that paired-pulse facilitation occurs before the chronic phase. The present data further support the view that hyperexcitability is present at an early stage of epileptogenesis. Network output is more facilitated during the latent than during the chronic period. Hyperexcitability may participate to epileptogenesis, but it is not sufficient in itself to produce seizures.     

Inhibition of corticosterone binding in vitro,in rabbit hippocampus,by chromatin bound aluminum

Summary Brains of patients with senile dementia of the Alzheimer type and with the dialysis encephalopathy syndrome, exhibit elevated aluminum levels. In Alzheimer's disease and in the experimental aluminum induced encephalopathy, intracellular aluminum is associated with nuclear chromatin. The work reported here was undertaken to test whether chromatin bound aluminum in hippoccampus of the rabbit interferes with nuclear binding of corticosterone-receptor complexes. The results showed that the mean binding of corticosterone decreased from 460±71 fmol/mg DNA in controls, to 343±81 fmol/mg DNA in hippocampal nuclei from aluminum treated rabbits, representing a decrease of 25%. This reduction occurred in the absence of aluminum induced neurofibrillary degeneration and indicates a possible functional consequence of the presence of aluminum on chromatin, and importantly, in the absence of morphological changes.Supported by the Ontario Mental Health Foundation and by Surrey Place Center     

Asymmetric uptake of 2-deoxy- -[C]glucose in the dorsal cochlear nucleus during Pavlovian conditioning in the rabbit

Uptake of 2-deoxy- -[¹⁴C]glucose was measured during Pavlovian conditioning of the rabbit's nictitating membrane response by both qualitative autoradiography and by quantitative measurement of radioactivity in samples of brain tissue. Conditioning was accomplished by pairing a tone stimulus delivered to both ears with an air-puff stimulus delivered to the right eye. Infusion of 2-deoxy- -[¹⁴C]glucose during the first day of conditioning when there was no evidence of acquisition or during the 7th day of conditioning when animals demonstrated 68% conditioned responses resulted in a significantly greater uptake of radioactivity by the caudal portions of the left as compared with the right dorsal cochlear nucleus. Similar changes were not observed in other auditory and non-auditory nuclei. Rabbits that had acquired conditioned responses across 6 days of training and were then exposed only to the tone-conditioned stimulus on the 7th day of testing exhibited 69% conditioned responses but no asymmetry in the uptake of 2-deoxy- -[¹⁴C]glucose. Control animals receiving unpaired presentations of tone and air puff or no stimulation did not acquire conditioned responses and did not demonstrate asymmetric uptake of radioactivity in the dorsal cochlear nucleus. These results indicate that the asymmetric uptake of radioactivity by the dorsal cochlear nucleus did not result from the effects of stimulation per se or the prior occurrence of learning but was due to the explicit pairing of the tone stimulus with the asymmetric delivery of the air puff. It would appear that the caudal dorsal cochlear nucleus not only serves as a signal transducer for auditory stimuli but also receives input from other sensory systems thus allowing it to both recognize when an auditory stimulus is followed by a biologically significant event and to transmit such information to other brain regions that are, in turn, responsible for learning.     

Ischemic Evidence of Transient Global Amnesia: Location of the Lesion in the Hippocampus

Background and purpose

Transient global amnesia (TGA) is a rare amnestic syndrome characterized by the sudden onset of a selective anterograde and retrograde amnesia with a time course of up to 24 hours. Recent studies have found a high frequency of small high-signal abnormalities in the hippocampus on diffusion-weighted imaging (DWI), and accordingly ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, which is known to be susceptible to ischemia.

Methods

Twenty consecutive patients with a clinical diagnosis of TGA underwent DWI both within 24 hours of symptom onset and 3 days later. Twenty patients with high-signal abnormalities in the hippocampus on the initial DWI underwent subsequent DWI and T2-weighted imaging in the coronal plane to precisely localize the lesions.

Results

Seventeen patients had small high-signal abnormalities (with diameters of 1-3 mm) in the hippocampus unilaterally on DWI. One of these patients had two lesions in one hippocampus. Three of the 20 patients had lesions bilaterally in the hippocampus, 1 of whom had 3 bilateral lesions. A total of 25 lesions were identified: 5 in the hippocampal head, 19 in the body, and 1 in the tail. Six patients had unilateral lesions on the left,11 patients had them on the right, and 3 patients had bilateral lesions.

Conclusions

In this study, lesions associated with TGA were localized mostly to the lateral portion of the hippocampus, corresponding to CA1. This finding supports the ischemic etiology of TGA, but the underlying pathophysiologic mechanism requires further investigation.     

Δ9-Tetrahydrocannabinol and the hippocampus: Effects on CA1 field potentials in rats

The effects of Δ⁹-tetiahydrocannabinol (THC) on ortho- and antidromically elicited CA1 field potentials were observed in locally anesthetized rats and in rats anesthetized with urethane. THC augmented amplitudes of population EPSP's as well as orthodromic and antidromic population spikes from pyramidal cells in locally anesthetized animals. Latencies to peak amplitude of these responses were increased. Conditioning-test shock experiments revealed that THC also depressed recurrent inhibition probably mediated by basket cells. In animals under urethane anesthesia THC enhanced test responses, but failed to augment population responses to the conditioning stimulus. It was concluded that THC enhanced postsynaptic excitatory processes but attenuated recurrent inhibition. Urethane anesthesia completely blocked the postsynaptic excitatory effect of THC but had little apparent influence on THC's disinhibitory action.     

Functional Transitions Between Epileptiform-Like Activity and Associative Memory in Hippocampal Region CA3

Clinical and experimental observations indicate that the hippocampus is critical in the formation of declarative memories. Interestingly, electrophysiological studies have demonstrated that the region also has a particularly low seizure threshold, where globally synchronous synaptic activity can occur. By using a detailed biophysical model of area CA3, it is shown how septal cholinergic modulation, through three distinct mechanisms, can interact with intrinsic and synaptic conductances to influence population behavior. A dissection of each mechanism demonstrates a variety of population firing activity ranging from fully synchronized behavior to a mixture of repetitive bursting and oscillations in reduced subsets of neurons, ideal for forming accurate associations during a learning and recall task.