Epilepsy is characterized by recurrent, spontaneous seizures and is a major contributor to the global burden of neurological disease. Although epilepsy can result from a variety of brain insults, in many cases the cause is unknown and, in a significant proportion of cases, seizures cannot be controlled by available treatments. Understanding the molecular alterations that underlie or are triggered by epileptogenesis would help to identify therapeutics to prevent or control progression to epilepsy.
View Article and Find Full Text PDFBrain-derived neurotrophic factor (BDNF) levels are elevated after status epilepticus (SE), leading to activation of multiple signaling pathways, including the janus kinase/signal transducer and activator of transcription pathway that mediates a decrease in GABAA receptor α1 subunits in the hippocampus (Lund et al., 2008). While BDNF can signal via its pro or mature form, the relative contribution of these forms to signaling after SE is not fully known.
View Article and Find Full Text PDFThe inferior olive (IO) is considered a crucial component of the eyeblink conditioning network. The cerebellar learning hypothesis proposes that the IO provides the cerebellum with a teaching signal that is required for the acquisition and maintenance of conditioned eyeblinks. Supporting this concept, previous experiments showed that lesions or inactivation of the IO blocked CR acquisition.
View Article and Find Full Text PDFIn the present paper, we examine the role of the cerebellar interpositus nucleus (IN) in motor and non-motor domains. Recent findings are considered, and we share the following conclusions: IN as part of the olivo-cortico-nuclear microcircuit is involved in providing powerful timing signals important in coordinating limb movements; IN could participate in the timing and performance of ongoing conditioned responses rather than the generation and/or initiation of such responses; IN is involved in the control of reflexive and voluntary movements in a task- and effector system-dependent fashion, including hand movements and associated upper limb adjustments, for quick effective actions; IN develops internal models for dynamic interactions of the motor system with the external environment for anticipatory control of movement; and IN plays a significant role in the modulation of autonomic and emotional functions.
View Article and Find Full Text PDFClassical conditioning of the eyeblink response in the rabbit is a form of motor learning whereby the animal learns to respond to an initially irrelevant conditioned stimulus (CS). It is thought that acquired conditioned responses (CRs) are adaptive because they protect the eye in anticipation of potentially harmful events. This protective mechanism is surprisingly inefficient because the acquisition of CRs requires extensive training - a condition that is unlikely to occur in nature.
View Article and Find Full Text PDFObjective: To determine if gait stability, as measured by harmonic ratios (HRs) derived from trunk accelerations, is improved during 3 amplitude-based cueing strategies (visual cues, lines on the floor 20% longer than preferred step length; verbal cues, experimenter saying "big step" every third; cognitive cues, participants think "big step") in people with Parkinson's disease.
Design: Gait analysis with a triaxial accelerometer.
Setting: University research laboratory.
The interposed nuclei (IN) of the intermediate cerebellum are critical components of the circuits that control associative learning of eyeblinks and other defensive reflexes in mammals. The IN, which represent the sole output of the intermediate cerebellum, receive massive GABAergic input from Purkinje cells of the cerebellar cortex and are thought to contribute to the acquisition and performance of classically conditioned eyeblinks. The specific role of deep cerebellar nuclei and the cerebellar cortex in eyeblink conditioning are not well understood.
View Article and Find Full Text PDFKinematic changes in Parkinson's disease (PD) gait are well documented; however, upper body dynamics are less understood. Harmonic ratios (HRs) measure the rhythm of trunk accelerations and can be examined in the vertical, anterior-posterior, and mediolateral planes, providing an indication of global walking stability (lower HR indicates poorer stability). We examined differences in HRs between persons with PD and healthy older adults and relationships between HRs and stride parameters.
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