Gait and upper limb variability in Parkinson's disease patients with and without freezing of gait.

Patients with Parkinson's disease (PD) and freezing of gait (FOG) (freezers) demonstrate high gait variability. The objective of this study was to determine whether freezers display a higher variability of upper limb movements and elucidate if these changes correlate with gait. We were the first group to compare directly objectively measured gait and upper limb movement variability of freezers between freezing episodes. Patients with objectively verified FOG (n = 11) and PD patients without FOG (non-freezers) (n = 11) in a non-randomized medication condition (OFF/ON) were analyzed. Uncued antiphasic finger tapping and forearm diadochokinetic movements were analyzed via three-dimensional ultrasound kinematic measurements. Gait variability of straight gait was assessed using ground reaction forces. Freezers had shorter stride length (p = 0.004) and higher stride length variability (p = 0.005) in the medication OFF condition. Movement variability was not different during finger tapping or diadochokinesia between the groups. There was a trend towards more freezing of the upper limb during finger tapping for the freezers (p = 0.07). Variability in stride length generation and stride timing was not associated with variability of upper limb movement in freezers. Our findings demonstrate that: (1) freezers have a higher spatial gait variability between freezing episodes; (2) freezing-like episodes of the upper limb occur in PD patients, and tend to be more pronounced among freezers than non-freezers for finger tapping; (3) spatial and temporal upper extremity variability is equally affected in freezers and non-freezers in an uncued task. Upper limb freezing is not correlated to lower limb freezing, implicating a different pathophysiology.

One-trial conditioning of aerial respiratory behaviour in Lymnaea stagnalis.

Repeated spaced training sessions of contingent tactile stimulation to the pneumostome as it opens are required to cause long-term memory (LTM) formation of aerial respiratory behaviour making if difficult to determine exactly when memory forms. We have devised a single-trial aversive operant conditioning training procedure in Lymnaea to be better able to elucidate the causal mechanisms of LTM formation. Observations of baseline breathing behaviour in hypoxia were first made. Twenty-four hours later the snails were trained using the single trial procedure, by placing them in a small Petri dish containing 4 ml of 25 mM KCl for 30-35s as soon as the first pneumostome opening in hypoxia was attempted. LTM was present if (1) breathing behaviour following training was significantly less than before; and (2) breathing behaviour post-training was significantly less in experimental groups than in yoked control groups. LTM persisted for 24 h but not 48 h. Yoked controls that received an aversive stimulus not contingent with pneumostome opening had no evidence of memory. Cooling directly after, but not at any other time, blocks LTM formation. LTM formation was also prevented by removal of the cell body of the neuron RPeD1 before training.

Stressful stimuli modulate memory formation in Lymnaea stagnalis.

Stress has been shown to be a strong modulator of learning and memory in animals. We employ operant training of aerial respiratory behaviour in our model system, the pond snail Lymnaea stagnalis, to show that application of an acute consistent physical stressor enhances memory formation. A single 30 min operant conditioning training session, which normally results in intermediate-term memory (ITM) persisting 3h, results in long-term memory (LTM) persisting 24h if immediately preceded or followed by a stressor, for example a 30s exposure to 25 mM KCl. Other physical stressors (0.3% quinine-HCl or quick cooling and warming) similarly enhance memory formation. The memory is context specific and is not seen after the application of too much or too little stress. The memory can be extinguished by exposing snails to the hypoxic training environment and withholding reinforcing stimuli. The LTM that results from 30 min of training and stressor exposure is dependent on de novo protein synthesis and gene transcription in a single neuron, RPeD1. Because the soma of RPeD1 must be present for memory augmentation by the application of a stressor we are well placed for future investigations to directly determine the specific molecular alterations by which stress primes the formation of LTM.