Biomedical subjects

M J Hardiman

Publications and source records attributed to M J Hardiman.

12 recordsLinked to original sources

PubMed1999

Cortical evoked potentials due to motion contrast in the blind hemifield.

Subcortical visual inputs to motion-selective cortex in primates survive after damage to the primary visual cortex (area 17/V1). Activation of human motion cortex was examined using scalp electrodes in a V1-damaged hemianope. Blind field motion-onset visual evoked potentials (VEPs) shared many of the characteristics associated with sighted vision but were smaller in amplitude and had longer latencies. The representative negative wave (C(II) peak) showed typical dependency on stimulus contrast, its peak latency increased and amplitude decreased as contrast decreased, reflecting the difficulty with which directional information could be detected. VEPs were present at contrasts below 25% when blind field motion was imperceptible even though direction guessing was paradoxically accurate. Subcortical inputs to motion cortex contribute to visual experience but not to conscious perception.

Adult↗

PubMed1996

Reversible inactivations of the cerebellum with muscimol prevent the acquisition and extinction of conditioned nictitating membrane responses in the rabbit.

Lesions of the cerebellum severely impair the classically conditioned nictitating membrane response (NMR) in rabbits. Thus, the cerebellum is essential for the production of conditioned responses (CRs), either because it is actively involved in NMR conditioning or because damage to it causes motor or other general deficits. To distinguish between these alternatives, the cerebellum may be inactivated during training. Inactivation of the cerebellum during acquisition training might result in the absence of CRs on initial trials of subsequent training without the neuronal blockade. The blockade may have prevented learning but it may have produced other deficits that require time or further training to overcome. This problem can be addressed by inactivating the cerebellum during extinction training. If inactivation during extinction training results in the immediate production of CRs when training is resumed without the blockade, then it may be concluded that extinction learning was prevented by the blockade-the presence of CRs argues against any deficits not associated with learning. We used muscimol to inactivate the cerebellum and test its involvement in acquisition and extinction of NMR conditioning in the same subjects. We injected muscimol close to the interpositus nucleus of the cerebellum 1 h before each of four daily training sessions of delay conditioning. Almost no CRs were produced in these training sessions-there was little or no acquisition of NMR conditioning during cerebellar inactivation. The subjects were then trained for four daily sessions without injections of muscimol. There were no CRs on initial trials of the first session of retraining, but all subjects produced CRs by the end of this session. The subjects then received four daily sessions of extinction training with muscimol inactivation of the nuclei-no CRs were produced. Extinction training then continued for four daily sessions without muscimol inactivation. On the first of these sessions, all subjects immediately produced high levels of CRs. These responses then extinguished within and between sessions with characteristic beginning-of-session spontaneous recovery. There was little or no extinction of NMR conditioning during cerebellar inactivation. After inactivation, the muscimol- inactivated subjects went on to acquire and extinguish NM responses at rates similar to those of appropriate controls. We conclude that cerebellar circuitry is essential for, and actively engaged in, both acquisition and extinction of this simple form of motor learning.

Animals↗

PubMed1992

Cerebellar cortex and eyeblink conditioning: a reexamination.

We examined the effects of cerebellar cortical lesions upon conditioned nictitating membrane responses in rabbits. Using extended postoperative conditioning and unpaired presentations of the conditioned stimuli (CSs), we confirmed that combined lesions of lobules HVI and ansiform lobe abolished conditioned responses (CRs) established to light and white noise CSs. Extended retraining enabled some slight recovery of CR frequencies. Less extensive cortical lesions produced initial abolition of CRs but allowed more complete recoveries. Although CR frequencies and amplitudes were profoundly depressed by cortical lesions, unconditioned response (UR) amplitudes to periorbital electrical stimulation were enhanced. The dissociation of lesion effects upon conditioned and unconditioned responses is consistent with the suggestion that cerebellar cortical mechanisms are important for the learning and execution of eyeblink conditioning.

Acoustic Stimulation↗

PubMed1989

Visual projections to the pontine nuclei in the rabbit: orthograde and retrograde tracing studies with WGA-HRP.

Visual projections to the pontine nuclei in the rabbit were examined by means of both orthograde and retrograde tracing of WGA-HRP. The tecto-pontine projection was examined following microinjections of WGA-HRP in the right superior colliculus. The projection to the pontine nuclei is strictly ipsilateral and terminates at middle and caudal levels of the pons. The projection is absent in rostral pontine nuclei. The strongest projection is to the dorsal border of the dorsolateral pontine nuclei and is the only projection seen when the primary injection site is confined to superficial laminae. When the primary injection site also includes intermediate and deep laminae, patches of labelled terminals are also seen within dorsolateral, lateral, peduncular, paramedian, and ventral pontine nuclei as well as in the contralateral nucleus reticularis tegmenti pontis. The striate corticopontine projection was also examined with orthograde tracing of WGA-HRP. The striate corticopontine projection is ipsilateral. Most labelled terminals were seen in dorsolateral and lateral pontine nuclei throughout the rostral half of pons with some additional terminal labelling in paramedian and peduncular nuclei. Labelled terminals were also seen in ventral pontine nuclei throughout the middle and caudal levels of the pons. In a retrograde tracing study, visual projections to the pontine nuclei were examined following microinjections of WGA-HRP into the pontine nuclei. Labelled cells were seen ipsilaterally in superficial and deep laminae of the superior colliculus and in layer V of striate and surrounding occipital cortex. The pontine nuclei also receive ipsilateral projections from the ventral lateral geniculate, the nucleus of the optic tract, anterior and posterior pretectal nuclei, and the dorsal and medial terminal nuclei of the accessory optic system. These pathways are potential sources of visual input to the cerebellum.

Animals↗

PubMed1987

Hippocampal lesions and trace conditioning in the rabbit.

Trace conditioning of the nictitating membrane response (NMR) was examined in rabbits with lesions of the dorsal hippocampus and fimbria-fornix. Using a white noise conditional stimulus and an electrical shock unconditional stimulus, the number and amplitude of conditional responses (CRs) was similar in hippocampus-lesioned and control subjects. At some stages of conditioning, the latencies of CRs from hippocampus-lesioned subjects were slightly shorter than those of the controls. We suggest that the hippocampus is not essential for trace conditioning but may exert a modulatory influence on the timing of the CR.

Animals↗

PubMed1986

Classical conditioning of the nictitating membrane response of the rabbit. IV. Lesions of the inferior olive.

The nictitating membrane response (NMR) of 15 rabbits was conditioned to light and white noise conditional stimuli (CSs) using a periorbital shock unconditional stimulus (US). Unilateral lesions of the inferior olive were then made. Lesions restricted to the medial parts of rostral dorsal accessory olive (DAO) and principal olive (PO) abolished conditioning and prevented subsequent acquisition on either side. Unconditional responses to the US were intact. Lesions in all other parts of the olive did not impair conditioning. The effective lesions were located in that part of the olive which supplies somatosensory information from the face to cerebellar lobule HVI. Lobule HVI is also essential for NMR conditioning. We suggest that this region of the inferior olive is part of a circuit which provides US information to the cerebellar cortex during NMR conditioning.

Animals↗

PubMed1985

Classical conditioning of the nictitating membrane response of the rabbit. I. Lesions of the cerebellar nuclei.

The classically conditioned nictitating membrane response (NMR) of the rabbit, a simple form of associative motor learning, is crucially dependent upon the cerebellum. Discrete unilateral lesions of the cerebellar nuclei were made in 20 rabbits. Lesions of the anterior interpositus nucleus (IA) abolished NMR conditioning to light and white noise stimuli on the side of the lesion without affecting unconditional responses. Lesions of the posterior interpositus nucleus, fastigial and dentate nuclei were without effect upon NMR conditioning.

Animals↗

PubMed1985

Classical conditioning of the nictitating membrane response of the rabbit. II. Lesions of the cerebellar cortex.

The nictitating membrane response (NMR) of 20 rabbits was conditioned to light and white noise conditional stimuli (CSs) using a periorbital shock unconditional stimulus (US). Unilateral lesions of the cerebellar cortex, sparing the underlying deep nuclei, were then made. Small lesions of cerebellar cortical lobule HVI abolished conditioning on the side of the lesion to both CSs leaving unconditional responses to the US intact. Larger lesions of the posterior lobe which spared HVI did not impair NMR conditioning. We conclude that cerebellar lobule HVI is essential for NMR conditioning in the rabbit. Degeneration following critical lesions of HVI was seen in a restricted region of the inferior olive - the medial part of the dorsal accessory olive and the adjoining medial part of the dorsal leaf of the principal olive. This region of the olive provides somatosensory information from the face to HVI. We suggest that HVI receives information related to the US via climbing fibres from the olive and CS information via mossy fibres from the pontine nuclei. The critical changes underlying NMR conditioning may be the association of these two inputs at the Purkinje cells of cortical lobule HVI.

Animals↗

PubMed1985

Classical conditioning of the nictitating membrane response of the rabbit. III. Connections of cerebellar lobule HVI.

We report the connections of cerebellar cortical lobule HVI in the rabbit. We have studied the anterograde and retrograde transport of wheatgerm-agglutinated horseradish peroxidase (WGA-HRP) following its injection into HVI to reveal efferent and afferent connections. All of the cases showed strong anterograde transport to the anterior interpositus nucleus (AIP) - indicating that this is the major efferent target of HVI. Retrogradely labelled cells were found in the inferior olivary, spinal trigeminal, lateral reticular, inferior vestibular and pontine nuclei. Within the olive, the medial part of the rostral dorsal accessory olive (DAO) and the adjacent medial part of the principal olive (PO) were consistently labelled in all cases. This area is known to receive somatosensory information from the face and neck. There was no projection to the hemispheral part of lobule VI from visual parts of the olive within the dorsal cap and medial parts of the medial accessory olive. Likely sources of visual and auditory information to HVI are the dorsolateral basilar pontine nuclei and nucleus reticularis tegmenti pontis, which were densely labelled in all cases. These anatomical findings are consistent with the suggestion that, during NMR conditioning, information related to the periorbital shock unconditional stimulus (US) may be provided by climbing fibres to HVI and light and white noise conditional stimulus (CS) information may be supplied by pontine mossy fibres.

Animals↗

PubMed1984

Trace conditioning of the nictitating membrane response in decorticate rabbits.

Rabbits with substantial neocortical lesions were given trace conditioning of the nictitating membrane response over a range of interstimulus intervals (ISIs). Unlike hippocampal lesioned animals, which show deficits in such conditioning, the decorticates were not impaired and they gave greater numbers of conditioned responses at longer ISIs than did sham-operated controls. These results suggest that a neocortical-entorhinal input to the hippocampus may not be crucial for trace conditioning.

Animals↗

PubMed1984

Discrete lesions of the cerebellar cortex abolish the classically conditioned nictitating membrane response of the rabbit.

The classically conditioned nictitating membrane response (NMR) of the rabbit is useful for analyses of brain structures and pathways involved in mammalian associative learning. Lesions of the entire cerebellum, its nuclei or its efferent pathway abolish conditioned NMR learning and prevent its reacquisition. Until now it has not been clear whether the cerebellar cortex is an essential part of the circuitry for NMR conditioning. Here we report that small lesions of the cerebellar cortex in the hemispheral portion of lobule VI, with sparing of the underlying nuclei, abolish the ipsilateral conditioned NMR and prevent it from being reacquired.

Animals↗

PubMed1983

Retention of conditioned inhibition of the nictitating membrane response in decorticate rabbits.

Rabbits were trained on a Pavlovian conditioned inhibition (CI) task using light as the reinforced conditional stimulus (CS) and the same light compounded with a tone as the non-reinforced CS. The conditional response was the nictitating membrane response (NMR). The subjects then received an extensive neocortical lesion or a sham operation. After 9 weeks postoperative recovery, the animals were retrained on the CI task. Sham operated control animals showed immediate and high levels of CI retention but the decorticates showed a profound initial loss, showing that there is a cortical influence in CI. Reacquisition of CI by the decorticates was rapid and showed considerable savings over de novo acquisition. This supports our earlier finding that the neocortex is not essential for the acquisition of CI.

Animals↗