Properties of Contextual Memory Formed in the Absence of αCaMKII Autophosphorylation

The alpha-isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is a major synaptic kinase that undergoes autophosphorylation after NMDA receptor activation, switching the kinase into a calcium-independent activity state. This αCaMKII autophosphorylation is essential for NMDA receptor-dependent long-term potentiation (LTP), induced by a single tetanus, in hippocampal area CA1 and in neocortex. Furthermore, the αCaMKII autophosphorylation is essential for contextual long-term memory (LTM) formation after a single training trial but not after a massed training session. Here, we show that in the absence of αCaMKII autophosphorylation contextual fear conditioning is hippocampus dependent and that multi-tetanus-dependent late-LTP cannot be induced in hippocampal area CA1. Furthermore, we show that in the absence of αCaMKII autophosphorylation contextual LTM persists for 30 days, the latest time point tested. Additionally, contextual, but not cued, LTM formation in the absence of αCaMKII autophosphorylation appears to be impaired in 18 month-old mice. Taken together, our findings suggest that αCaMKII autophosphorylation-independent plasticity in the hippocampus is sufficient for contextual LTM formation and that αCaMKII autophosphorylation may be important for delaying age-related impairments in hippocampal memory formation. Furthermore, they propose that NMDA receptor-dependent LTP in hippocampal area CA1 is essential for contextual LTM formation after a single trial but not after massed training. Finally, our results challenge the proposal that NMDA receptor-dependent LTP in neocortex is required for remote contextual LTM

Neural model of dopaminergic control of arm movements in Parkinson’s disease bradykinesia

Patients suffering from Parkinson’s disease display a number of symptoms such a resting tremor, bradykinesia, etc. Bradykinesia is the hallmark and most disabling symptom of Parkinson’s disease (PD). Herein, a basal ganglia-cortico-spinal circuit for the control of voluntary arm movements in PD bradykinesia is extended by incorporating DAergic innervation of cells in the cortical and spinal components of the circuit. The resultant model simulates successfully several of the main reported effects of DA depletion on neuronal, electromyographic and movement parameters of PD bradykinesia

The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation

The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable

Evidence for a monosynaptic mechanism in the tonic vibration reflex of the human masseter muscle.

Vibration of the masseter and temporalis muscles in normal human adult subjects elicits a tonic vibration reflex with unexpected features. The electromyographic response is not asynchronous as in the limb muscles, but involves well-defined spikes with a one-to-one temporal relation to the vibration cycles. The effect of various parameters such as muscle stretch, vibration frequency or amplitude, etc, has been investigated. The small latency fluctuation of the vibration-induced spikes is compatible with a monosynaptic reflex mechanism which is considered to be assisted by a polysynaptic facilitatory background of proprioceptive origin

Disabling of the oculomotor neural integrator by kainic acid injections in the prepositus-vestibular complex of the cat.

1. This study was intended to test the candidature of the prepositus-vestibular nuclear complex for being the location of the oculomotor neural integrator (Robinson's integrator). 2. Microinjections of kainic acid (2 micrograms dissolved in 1 microliter) were made in awake cats. Injection sites were located either in the prepositus hypoglossi nucleus (p.h.), the medial vestibular nucleus (m.v.n.), the medial longitudinal fasciculus (m.l.f.) or in the magnocellular tegmental field of the reticular formation. 3. Theory predicts that a complete disabling of the neural integrator will cause (a) an exponential post-saccadic drift whose time constant will be 0.16 s in the dark (b) a phase lead of +93 deg as the vestibulo-ocular reflex is tested at 0.10 Hz in the dark and (c) a nearly complete abolition of the optokinetic nystagmus (o.k.n.). 4. About 1 h after a unilateral kainic acid injection in the p.h., we observed (a) a large bilateral post-saccadic drift (time constant sometimes as low as 0.2 s) (b) a large phase lead at 0.10 Hz (range: from +69 to +98 deg) (c) an abolition of the o.k.n. control injection of phosphate buffer in the p.h. did not produce any deficit. 5. A unilateral kainic acid injection in the m.v.n. induced a nystagmus followed by signs of bilateral failure of the neural integrator similar to those observed after kainic acid injection in the p.h. 6. Injection near the mid-line, between the two p.h. nuclei, induced a defect of the neural integrator less than that observed after kainic acid injection in either the p.h. or the m.v.n. Injection of kainic acid in the magnocellular tegmental field of the reticular formation did not produce any sign of failure of the neural integrator. No post-saccadic drift was observed. 7. We have concluded that (a) the p.h. nucleus is involved in the integration processing, and that (b) the m.v.n. is involved either in the integration processing or in the relaying of the output of the neural integrator to the oculomotoneurones

Ballistic contractions in man: characteristic recruitment pattern of single motor units of the tibialis anterior muscle.

1. Single motor units were recorded with highly selective electrodes from intact tibialis anterior muscle in the adult man. A detailed parametric analysis was made of the discharge patterns during voluntary isometric contractions of different peak forces carried out at various rates of force development. 2. During the smooth tracking of a ramp force, the different motor units recorded from a given muscle site were recruited in a consistant order, each unit becoming active when the muscle developed a certain level of force. The threshold of some of the units in such slow ramp contractions exceeded 8 kg. By contrast, in brisk ballistic contractions reaching a peak force of 12 kg in less than 0-15 sec, the same motor units discharged in a transient burst which largely preceded the muscle force production. 3. In slow tracking ramp contractions, the instantaneous frequency of single motor units was initially rather low (5-15/sec) and it increased as the ramp force augmented. By contrast, in (strong) ballistic contractions, the same units discharged at an unusually high instantaneous frequency (60-120/sec) early in the burst and the firing frequency decreased thereafter. Such hitherto unknown pattern appears characteristic of ballistic contractions and it was not found in even fast tracking ramp contractions achieving 12 kg in only 0-4 sec. 4. The potentials of the different motor units activated are rather crowded at intervals of a few msec in the early burst of a strong ballistic contraction and observations on the rank activation of the different motor units do not provide reliable data for the analysis of the recruitment order of units in ballistic contractions. 5. A new method is described for estimating ballistic force threshold of single motor units. When a large series of brisk ballistic contractions with peak forces ranging from 0-05 to 12 kg was carried out any given motor unit only became active when the ballistic peak force exceeded a certain reproducible value. A detailed analysis of the recruitment order based on these ballistic force thresholds showed it to be virtually identical to the recruitment order of the same units in slow tracking ramp contractions (correlation=0-95). 6. Ballistic contractions are graded in force both by the recruitment of additional motor units in stronger contractions, and by an increase in their rate of firing. These gradation mechanisms are discussed

The hypothesis of the uniqueness of the oculomotor neural integrator: direct experimental evidence in the cat.

1. As far as horizontal eye movements are concerned, the well-known hypothesis, not yet experimentally proved, of the common neural integrator states that the eye-position signal is generated by a common network, regardless of the type of versional movement. The aim of this study was to evaluate the validity of this hypothesis by checking whether the sensitivity to eye position of the neurones of the nucleus prepositus hypoglossi (NPH) (the main component of the system integrating the different incoming velocity signals) would be the same regardless of the type of versional movement. 2. The discharge of sixty-five NPH neurones was recorded in the alert cat during spontaneous eye movements made in the light and in response to sinusoidal rotations of the head in complete darkness. 3. For each NPH neurone, the sensitivity to eye position was determined from measurements carried out during intersaccadic fixation. The discharge rate of the studied neurone was plotted against eye position. The slope of the resulting regression line gave the sensitivity (measured during intersaccadic fixation in the light) of the neurone to eye position, which was termed K(f). 4. A new method was developed to measure the sensitivity to eye position (K(v)) of neurones during vestibular slow phases. The difficulty came from the fact that, during slow phases, eye velocity and eye position changed simultaneously and that each of those two variables could influence neuronal activity. For each neurone, the instantaneous firing rate was measured each time the eye passed through a given position during any slow phase generated during any vestibulo-ocular reflex. At a given position, the discharge rate of the neurone under study was plotted against the eye velocity. From the resulting linear regression line, two interesting values were obtained: its slope, corresponding to the sensitivity of the neurone to eye velocity, R(v), (at that given eye position) and its 'y'-intercept, F(0), the interpolated firing rate when the eye velocity was zero. This procedure was repeated for different eye positions. The values of F(0) were then plotted against the eye positions. The slope of the resulting regression line gave the sensitivity (measured during vestibular stimulation) of the neurone to eye position, which was termed K(v). 5. The errors on the individual values of K(f) and K(v) were assessed in order to allow a statistical comparison at the single unit level. 6. We found that, for each of our sixty-five neurones, the sensitivity to eye position measured during intersaccadic fixation in the light was equal to the sensitivity to eye position measured during the vestibulo-ocular reflex (VOR) elicited in complete darkness. We conclude that our results favour the hypothesis of a unique horizontal oculomotor integrator for all versional movements

Vibration-induced discharge patterns of single motor units in the masseter muscle in man.

Single motor unit potentials were recorded with small bipolar wires from intact masseter muscles in the adult man and a detailed parametric analysis of the effects of muscle vibration on motor unit discharges was carried out. 2. When the vibration amplitude was kept constant, each unit started firing at a definite threshold of vibration frequency. With higher frequencies the rate of firing rapidly reached a maximum. Units recruited at higher frequencies presented a lower maximum rate of firing. 3. When the vibration frequency was kept constant, each masseter unit discharged at a definite threshold of vibration amplitude. With higher amplitudes the unit quickly reached a maximum rate of discharge. Units with a higher frequency threshold tended to also present a higher amplitude threshold. Motor unit "excitability" curves could be plotted using the combined threshold conditions for frequency and amplitude of applied vibrations. 4. With a given parametric set of vibration, the units only started firing at a given delay after the onset of vibration. The delay was quite different for different units and it increased considerably, sometimes by several seconds, when the vibration amplitude was made smaller. 5. In all the experimental conditions tested, and even when the unit discharge did not start until several seconds after vibration onset, the unit potential presented a close and highly consistent temporal relation to the vibration cycles. The slow recruitment process is thought to involve a polysynaptic excitatory mechanism which progressively depolarizes the masseter motoneurones close to their threshold, the actual firing being triggered by monosynaptic excitatory post-synaptic potentials from I(a) afferents, hence the small latency jitter recorded. This special pattern of tonic vibration reflex in jaw-closing muscles in man may result from the lack of reciprocal inhibition from the jaw-opening muscles