Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine,captopril, CGP 37 849, and strychnine in mice

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37 849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37 849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.     

Neural plasticity in vivo: opioid sensitivity of memory develops gradually after a septal lesion

Neuronal plasticity can manifest itself in alterations in the sensitivity of memory to the effects of drugs. After the production of a brain lesion, the memory processing of a passive-avoidance task in mice gradually becomes sensitive to the effect of morphine, i.e., an improvement in retention performance is seen after 6 weeks, but not after 1 or 2 weeks. The results presented demonstrate that, even if they lead to no discernible changes in behaviour, plastic processes can still be detected by means of behavioural tests.     

Effect of electrical cutaneous stimulation on the level of succinate dehydrogenase activation and changes in glutamatergic synaptic transmission in response to sensory stimulation

It is shown that the rise of succinate dehydrogenase activity in the hippocampus depends on the number of sensory stimuli presented before decapitation, which correlates with changes in the efficiency of glutamatergic synaptic transmission in hippocampal sections from the same animal. Electrocutaneous stimulation potentiates the activation of succinate dehydrogenase induced by sensory stimulation probably due to enhanced glutamate release. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 4, pp. 404–407, April, 1997     

A glass/silicon composite intracortical electrode array

A new manufacturing technique has been developed for creating silicon-based, penetrating electrode arrays intended for implantation into cerebral cortex. The arrays consist of a 4.2 mm×4.2 mm glass/silicon composite base, from which project 100 silicon needle-type electrodes in a 10×10 array. Each needle is approximately 1,500 μm long, 80μm in diameter at the base, and tapers to a sharp point at the metalized tip. The technique used to manufacture these arrays differs from our previous method in that a glass dielectric, rather than ap-n-p junction, provides electrical isolation between the individual electrodes in the array. The new electrode arrays exhibit superior electrical properties to those described previously. We have measured interelectrode impedances of at least 10¹³ Ω, and interelectrode capacitances of approximately 50 fF for the new arrays. In this paper, we describe the manufacturing techniques used to create the arrays, focusing on the dielectric isolation technique, and discuss the electrical and mechanical characteristics of these arrays.     

Riluzole suppresses motor cortex facilitation in correlation to its plasma level

The aim of our study was to measure the effects of the glutamate antagonist riluzole on different parameters of motor excitability, using transcranial magnetic stimulation (TMS) during 7 days of riluzole administration, and to correlate these effects with riluzole plasma levels. Nine healthy volunteers received a dose of 100 mg riluzole from day 1 to 7 of the study period. Electrophysiological examinations were performed on day 1 before and 2 h, 5 h and 8 h after riluzole administration, on day 2, day 3 and day 5 before riluzole administration, and on day 8. Plasma samples were taken simultaneously. The excitability of the motor cortex, supraspinal and spinal motor pathways was tested by studying intracortical facilitation and inhibition, the cortical silent period and motor threshold after TMS, as well as the peripheral silent period and F-wave amplitudes after electrical peripheral nerve stimulation. We found a significant reduction of intracortical facilitation, which correlated significantly with riluzole plasma levels. To a lesser extent, intracortical inhibition was enhanced on day 1, motor threshold was increased on day 8 and F-wave amplitudes were reduced. These changes did not correlate with riluzole plasma levels. We conclude that the main effect of riluzole in vivo is a reduction of intracortical facilitation, which is closely related to the drug's level in the plasma. The most probable mechanism involves an effect on glutamatergic synaptic transmission.     

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey

Summary Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4–20 A, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 A, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 A. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 A respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different muscle fields. The merits of STA and ICMS for exploring cortical organisation are discussed.     

Disorder in reciprocal innervation upon initiation of voluntary movement in patients with Parkinson's disease

Summary Reciprocal innervation of the soleus motoneurones upon initiation of voluntary ankle dorsiflexion was investigated in eight patients with Parkinson's disease. H-reflex and visually guided step tracking methods were used for testing moto-neurone excitability and for controlling the timing of movement initiation, respectively. While reciprocal inhibition appeared almost simultaneously with the agonist electromyographic (EMG) onset in normal subjects (Kagamihara and Tanaka 1985), facilitation appeared in the majority of patients under the same onset condition. It increased slowly, reaching a maximum at about 100 ms after the EMG onset. It then subsided slowly at around 200–300 ms, and was replaced thereafter by an inhibitory effect. No coactivation of the soleus muscle was detected electromyographically. The facilitation between the EMG onset and the onset of mechanical contraction was attributed to the direct effect of the descending command from the brain, suggesting a certain disorder in controlling the system for reciprocal innervation.     

Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions

The present study aimed to further investigate whether the intracortical neural circuits within the primary motor cortex (M1) are modulated during ipsilateral voluntary finger movements. Single- and paired-pulse (interstimulus intervals, ISIs; 3 ms and 12 ms) transcranial magnetic stimulations of the left M1 were applied to elicit motor evoked potential (MEP) in the right first dorsal interosseous (Rt-FDI) muscle during voluntary contractions (10% and 30% maximum voluntary contraction) of the left FDI (Lt-FDI) muscle. F-waves of Rt-FDI muscle were recorded under these left index-finger conditions for ensuring that the excitability changes occur at the supraspinal level. MEPs were also recorded during motor imagery of the left index-finger abduction instead of overt movement. The results showed that, in single-pulse transcranial magnetic stimulation (TMS) paradigm, MEPs in Rt-FDI muscle were markedly enhanced during voluntary contractions of Lt-FDI muscle compared with the complete resting state. In paired-pulse TMS paradigm, the short intracortical inhibition was significantly reduced in proportion to increments of the ipsilateral muscle contraction, whereas the intracortical facilitation had no change. F-wave of Rt-FDI muscle was unchanged under these conditions, while MEP in Rt-FDI muscle was also enhanced during motor imagery of the left index-finger abduction. Based on the present results, it is suggested that the intracortical inhibitory neural circuits may be modulated in the transition from rest to activity of the ipsilateral homonymous muscle. The excitability changes in M1 might be induced by overflows of voluntary drive given to the ipsilateral limb, probably via the transcallosal pathway.     

Maturation of Startle Modulation

This study of the maturation of prestimulation-induced modulation of startle in 3 to 8 year old children and adults demonstrated significant effects of age on both startle magnitude and onset latency. Startle was evoked by 104dB(SPL) 50-ms bursts of white noise, and the amplitude and onset latency of the blink reflex were measured after integration of the obicularis oculi EMG. Prestimulation with 75dB 1000 Hz tones resulted in severe inhibition of both amplitude and latency in adults when 20-ms tones preceded the startling stimuli by 120 ms or 250 ms. Following sustained prestimulation for 2000 ms, the adults showed modest nonsignificant response facilitation. Eight-year-old children showed mature inhibitory and facilitatory startle amplitude modulation, but significantly less inhibition and more facilitation of onset latency compared to adults. Preschool children showed significantly less amplitude and latency inhibition and more facilitation than 8-year-olds and adults. In response to prestimulation 120 ms before startling stimuli, the preschool children actually showed latency facilitation. Modulation of startle by prestimulation is mediated by brainstem neuronal networks. These findings suggest that brainstem mechanisms which mediate startle response modulation undergo development during early childhood and do not mature until about 8 years of age.