Conditioned and unconditioned forelimb reflex systems in the cat: involvement of the intermediate cerebellum

 Temporary inactivation of the cerebellar interposed nuclei was used to assess the role of the intermediate cerebellum in the performance of forelimb cutaneo-muscular reflexes in the cat. The following types of reflexive responses were evaluated: the classically conditioned and unconditioned forelimb withdrawal responses and the forelimb tactile placing, hopping and magnet responses. The experiments tested the hypothesis that the intermediate cerebellum is involved in the performance of all the above forelimb reflexes. The forelimb withdrawal reflex was classically conditioned in a newly developed paradigm in which animals were first operantly conditioned to stand on four elevated platforms. Trained animals were microinjected with a γ-aminobutyric acid (GABA) agonist, muscimol, in the interposed nuclei, and the effects of inactivation of the intermediate cerebellar output on the forelimb reflexes were examined. The main findings of these experiments are that unilateral muscimol inactivation of the interposed nuclei in the cat abolished the expression of the classically conditioned limb flexion reflex, suppressed the performance of the unconditioned withdrawal reflex and, in parallel, downregulated the tactile placing, hopping and magnet postural responses in the ipsilateral forelimb. These observations are inconsistent with concepts indicating exclusive involvement of the intermediate cerebellum in the classically conditioned reflexes elicited by aversive stimuli. On the contrary, they support the hypothesis of a more global involvement of this structure in learned and unlearned defensive flexion reflexes and in automatic postural response systems. Received: 29 July 1996 / Accepted: 26 September 1996     

Effects of calcium and calcium-channel blocker methoxyverapamil on the beta-adrenoceptors in myocardial cells in vitro.

The possible relationship between methoxyverapamil (D600) as a calcium-channel blocker and the beta-adrenoceptors was investigated on heart cells grown in culture, using [3H]CGP-12177 as a radioligand. Treatment with D600 (20 micrograms/mL) for 24 hr caused a decrease of 30% in the [3H]CGP-12177 binding sites. Scatchard analysis showed that the Bmax is similar in control and D600-treated cells, but the Kd in D600-treated cells increases. The effect of D600 on the isoproterenol-induced adenylate cyclase activation was examined and it was found that the D600 prevented the increase in cAMP obtained by isoproterenol treatment. These results indicate that the action of D600 on the beta-adrenoceptors is a competitive inhibition of the [3H]CGP-12177 binding sites. We investigated the effect of Ca2+ in the growth medium on the level of beta-adrenoceptors. Heart cells grown for 24 hr in Ca(2+)-free medium showed a decrease of 36% in the [3H]CGP-12177 binding sites without changing the dissociation constant. This decrease is probably a result of reduction in synthesis of the receptors. The level of receptors returned to control values following replenishment with normal growth medium. These results show that calcium is essential for the development of the beta-adrenoceptors in heart cells in vitro.     

Expression of amoebapores is required for full expression of Entamoeba histolytica virulence in amebic liver abscess but is not necessary for the induction of inflammation or tissue damage in amebic colitis

Entamoeba histolytica trophozoites produce amoebapores, a family of small amphipathic peptides capable of insertion into bacterial or eukaryotic membranes and causing cellular lysis. Recently, E. histolytica trophozoites that are totally deficient in the production of amoebapore-A were created through a gene silencing mechanism (R. Bracha, Y. Nuchamowitz, and D. Mirelman, Eukaryot. Cell 2:295-305, 2003). Here we tested the virulence of amoebapore A(-) trophozoites in models of the two major forms of amebic disease: amebic liver abscess and amebic colitis. We demonstrate that amoebapore expression is required for full virulence in the SCID mouse model of amebic liver abscess, but E. histolytica trophozoites that do not express amoebapore-A can still cause inflammation and tissue damage in infected human colonic xenografts. These data are consistent with the concept that tissue damage may proceed by different mechanisms in amebic liver abscess compared to amebic colitis.     

On-line compensation for perturbations of a reaching movement is cerebellar dependent: support for the task dependency hypothesis

Although the cerebellum has been shown to be critical for the acquisition and retention of adaptive modifications in certain reflex behaviors, this structures role in the learning of motor skills required to execute complex voluntary goal-directed movements still is unclear. This study explores this issue by analyzing the effects of inactivating the interposed and dentate cerebellar nuclei on the adaptation required to compensate for an external elastic load applied during a reaching movement. We show that cats with these nuclei inactivated can adapt to predictable perturbations of the forelimb during a goal-directed reach by including a compensatory component in the motor plan prior to movement initiation. In contrast, when comparable compensatory modifications must be triggered on-line because the perturbations are applied in randomized trials (i.e., unpredictably), such adaptive responses cannot be executed or reacquired after the interposed and dentate nuclei are inactivated. These findings provide the first demonstration of the condition-dependent nature of the cerebellums contribution to the learning of a specific volitional task.     

Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization

A number of consistent clinical observations provide direction for the hypothesis that pathological sensitization of neuronal systems may be an important factor for relapse or the onset of stimulant-induced psychosis (eg, methamphetamine or amphetamine psychosis, cocaine psychosis and phencyclidine psychosis) and schizophrenia. First, psychotic symptoms can be produced in normal subjects by stimulants. Secondly, a large portion of schizophrenic patients exhibit exacerbation of psychotic symptoms in response to stimulants at doses which would not be psychotogenic in normal subjects. Lastly, the ability of stress to precipitate the onset and relapse of schizophrenia is well documented. In this regard, acute responses to stimulants provide useful information for relapse prediction of schizophrenia and substance abuse. This paper addresses the nature and role of pathological sensitization in relapse of stimulant- and phencyclidine-induced psychosis and schizophrenia, and its relation to pathophysiology of schizophrenia.     

Subtle signs of prenatal maldevelopment of the hand ectoderm in schizophrenia: a preliminary monozygotic twin study

Genes that predispose to psychosis may act by making individuals more vulnerable to the disruptive effects of various prenatal insults. Fetal organogenesis is mostly completed in the first prenatal trimester. The second trimester is a critical period of massive neuronal migration from the periventricular germinal matrix to the cortex. A peripheral appendage developing simultaneously with this neural migration to the cortex is the distal upper limb. The ectodermal cells of the fetal upper limb migrate to form the hand skin during the fourth and fifth months of gestation (first two-thirds of the second prenatal trimester). Discrepancies in hand morphology between two identical (monozygotic [MZ]) co-twins may be temporal markers, that is, the "fossilized" evidence of various ischemic and other nongenetic insults that may have affected one fetus more than his MZ co-twin during that early part of the second trimester. In twins, prenatal insults (e.g., ischemia) frequently do not affect both co-twins to the same extent, so we examined seven putative markers of prenatal injury to the hand in 24 MZ twin pairs discordant for schizophrenia or delusional disorder. Compared with well co-twins, the affected co-twins had significantly higher total scores of fourth- and fifth-month dysmorphological hand anomalies.     

Independence in self-care activities in children with myelomeningocele: exploring factors based on the International Classification of Function model

Purpose: To investigate the relationship between disease factors, body functions and structures, activities, personal and environmental factors with independence in self-care activities in children with myelomeningocele (MMC), utilizing the International Classification of Function model.

Method: 113 children with MMC, aged 3–18 years were assessed during an annual MMC-clinic visit. Data on the personal and environmental factors, disease factors, hand function, mobility, visual perception, cognition, and communication were assessed in relation to the Pediatric Evaluation of Disability Inventory (PEDI) self-care domain.

Results: The mean PEDI caregiver assistance score was 22.1 (ranged between <10 and 62) well below the norms. The most significant determinant of dependence in self-care activities was the presence of hydrocephalus, a child with hydrocephalus scored a mean of 9.2 points less on the PEDI caregiver scale (p?=?0.02). By using a linear regression, the most significant factors associated with the PEDI scores among children with hydrocephalus were the age of the child, function of the non-dominant hand, ambulation, and cognitive function.

Conclusion: In children with MMC the presence of hydrocephalus appears to be more significantly associated with functional independence than the neurological level. The International Classification of Function model provides an in-depth multidisciplinary model that facilitates in investigating independence in self-care activities in children with MMC. It is important to take personal factors and various functional impairments into account when working with these children to promote independence.

• Implications for Rehabilitation

• When working with children with myelomeningocele on independence in daily living activities, it is necessary that health professionals demonstrate a holistic view of the child and his/her disability.

• Health professionals should take into account information on all factors of the International Classification of Function, in order to help the children, achieve maximal independence.

• It is important for health professionals to consider presence or lack of hydrocephalus when working with children with myelomeningocele to achieve functional gains.

• Improving upper extremity function and cognitive ability in children with myelomeningocele may help promote independence in activities of daily living.

• It is necessary for health professionals to continue to work with children with myelomeningocele on maximizing independence as they get older, for it is possible for them to achieve independence at a later age.

• While this study did not explore participation, this is an essential part of the International Classification of Function and is generally related to function. Participation allows a child to be involved in life situations, contributes to life satisfaction and prepares children for critical adult roles. It is therefore important to assess and monitor this measure. Further studies should examine associations between independence in self-care activities and participation.