Body temperature control in rats by muscle tone during rest or sleep.

AIM: To explore the role of tonic motor unit activity in body temperature control. METHODS: Motor unit activity in soleus and several other skeletal muscles was recorded electromyographically from adult rats placed in a climate chamber on a load sensitive floor, which, together with video monitoring, allowed detection of every successive period of movement and no movement. RESULTS: In the absence of movements during rest or sleep, motor unit activity was exclusively tonic and therefore equivalent to muscle tone as defined here. The amount of tonic activity increased linearly in the soleus as the ambient temperature decreased from 32°C to below 7°C, owing to progressive recruitment and increased firing rate of individual units. Brief movements occurred randomly and frequently during rest or sleep in association with brief facilitation or inhibition of motor neurons that turned tonic motor unit activity on or off, partitioning the tonic activity among the available motor units. Shivering first appeared when a falling ambient temperature reached ≤7°C in several muscles except soleus, which was as active between shivering bursts as during them. CONCLUSION: Muscle tone and overt shivering are strikingly different phenomena. Tonic motor unit activity in the absence of movements evokes isometric contractions and, therefore, generates heat. Accordingly, when the amount of tonic activity increases with falling ambient temperature, so must heat production. Consequently, graded muscle tone appears as an important and independent mechanism for thermogenesis during rest or sleep at ambient temperatures ranging from <7°C to at least 32°C.

A proposed tandem mechanism for memory storage in neurons involving magnetite and prions.

Knowledge about how information is stored in neurons of animals and in the human brain is still incomplete. A hypothesis related to long-term changes in synaptic efficiency has strong experimental support, but does not seem to be able to explain all observations. It has recently been proposed that magnetite together with a prion-like protein could be involved in a tandem mechanism for storage of memory in neurons in which electric impulses are received and reshaped by the magnetite to a form which can be accepted by the protein. The magnetite crystals can be magnetized by an electrical impulse, but they cannot hold the magnetism, which drops to zero after each impulse. Therefore, magnetite cannot be the substance in which information is stored. In the present paper we explain how a tandem mechanism could function in a neuron in which magnetite is situated together with a prion-like protein close to the cell surface membrane of the axon. We assume in addition that the information is stored in special storage neurons. With this, we propose a new hypothesis for information storage in neurons which could operate in addition to synaptic plasticity, but perhaps in different neurons.

Glutamatergic modulation of synaptic-like vesicle recycling in mechanosensory lanceolate nerve terminals of mammalian hair follicles.

Our aim in the present study was to determine whether a glutamatergic modulatory system involving synaptic-like vesicles (SLVs) is present in the lanceolate ending of the mouse and rat hair follicle and, if so, to assess its similarity to that of the rat muscle spindle annulospiral ending we have described previously. Both types of endings are formed by the peripheral sensory terminals of primary mechanosensory dorsal root ganglion cells, so the presence of such a system in the lanceolate ending would provide support for our hypothesis that it is a general property of fundamental importance to the regulation of the responsiveness of the broad class of primary mechanosensory endings. We show not only that an SLV-based system is present in lanceolate endings, but also that there are clear parallels between its operation in the two types of mechanosensory endings. In particular, we demonstrate that, as in the muscle spindle: (i) FM1-43 labels the sensory terminals of the lanceolate ending, rather than the closely associated accessory (glial) cells; (ii) the dye enters and leaves the terminals primarily by SLV recycling; (iii) the dye does not block the electrical response to mechanical stimulation, in contrast to its effect on the hair cell and dorsal root ganglion cells in culture; (iv) SLV recycling is Ca(2+) sensitive; and (v) the sensory terminals are enriched in glutamate. Thus, in the lanceolate sensory ending SLV recycling is itself regulated, at least in part, by glutamate acting through a phospholipase D-coupled metabotropic glutamate receptor.

A microcapsule technique for long-term conduction block of the sciatic nerve by tetrodotoxin.

Tetrodotoxin (TTX) is a selective blocker of voltage-gated Na+ channels that is used to block action potentials in vitro and in vivo. Maintaining a sufficiently high local concentration of TTX in vivo to block conduction in a peripheral nerve is technically demanding and carries a risk of systemic toxicity. We report that slow diffusion of TTX out of a microcapsule (glass capillary) inserted beneath the epineurium of the sciatic nerve, with a loose cuff around the nerve, combines high blocking efficacy with low systemic toxicity in rats and mice. The local anaesthesia and motor paralysis was stable for at least 4-6 weeks. The conduction block was reversible and did not cause any obvious nerve injury. Low cost and simple surgical implementation make this new system an interesting alternative to existing long-term drug delivery methods.

Preserved granulocyte formation and function, as well as bone marrow innervation, in subjects with complete spinal cord injury.

Patients with a spinal cord injury are at risk of infections and is partly attributed to immobilization. Their lymphocyte-mediated immunity is impaired and the growth of blood progenitor cells is reduced. An adequate immune response depends on granulocytes being mobilized rapidly and activated properly, at the inflammatory site. Possibly this requires a coordinated interaction between the autonomous nervous system and cells within the haematopoietic bone marrow. Granulocyte function in the spinal cord injured has not been evaluated. Although there is evidence that the bone marrow in rodents is innervated, it is uncertain whether human bone marrow is similarly affected. Microscopy and immunolabelling followed by flow cytometry, showed that blood and bone marrow counts of leucocyte subsets were similar in paraplegic, tetraplegic and control subjects (P > 0.05). Neutrophilic migration and oxygen consumption, as well as eosinophil activation, assayed as release of eosinophilic cationic protein or CD69 expression, were not altered after spinal cord injury (P > 0.05). Cryostat sections of human bone marrow biopsies stained positive with glyoxylic acid, indicating the presence of catecholamine-containing nerves in both the patients and the controls. We conclude that terminal differentiation and formation of granulocytes, as well as their functional capacity, do not depend appreciably on supraspinal nervous regulation.

Activity-dependent plasticity of transmitter release from nerve terminals in rat fast and slow muscles.

Neuromuscular junctions (NMJs) on fast and slow muscle fibers display different transmitter release characteristics that appear well adapted to the different patterns of nerve impulses that they transmit in vivo. Here, we ask whether the release properties of such NMJs, termed fast and slow, can be transformed by chronic nerve stimulation. In young adult rats, nerve impulse conduction in the sciatic nerve was blocked by TTX, and the nerve to the fast extensor digitorum longus (EDL) or the slow soleus (SOL) muscle stimulated directly below the block with slow (20 Hz for 10 sec every 30 sec) or fast (150 Hz for 1 sec every 60 sec) stimulus patterns, respectively. After 3-4 weeks, originally fast EDL-NMJs and slow SOL-NMJs had become almost fully transformed to slow and fast NMJs, respectively, with respect to maintenance of transmitter release during tonic 20 Hz stimulation in vitro and ratio of quantal content to vesicle pool size. TTX block alone had no such transforming effect. Vesicle recycle time was unaffected by the stimulation, whereas initial quantal content and vesicle pool size were reduced (by 49% and 57% in EDL and 33% and 67% in SOL). Muscle fiber diameter also declined (by 49% in EDL and 33% in SOL vs 46% in unstimulated SOL; unstimulated EDL was not examined). We conclude that fast and slow NMJs display marked plasticity by being able to adapt important release characteristics to the impulse patterns imposed on them.

Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors.

We report that functional subtypes of spinal motoneurons and skeletal muscle fibers can be selectively transduced using replication-defective adenoviral (ADV) or adeno-associated (AAV) viral vectors. After intramuscular injection in adult rodents, ADV vectors transduced both fast-twitch and slow-twitch skeletal muscle fibers. Intramuscular injection of ADV vectors also caused transduction of spinal motoneurons and dorsal root ganglion cells. However, only neurons innervating the injected muscle were transduced, as shown by co-injection of a retrograde axonal tracer. In adult male rats it is therefore possible to transduce fast or slow spinal motoneurons and muscle fibers selectively since in these animals, the extensor digitorum longus and soleus muscles contain almost exclusively fast or slow motor units, respectively. In rats, AAV vectors transduced muscle fibers in the predominantly fast extensor digitorum longus but not in the predominantly slow soleus muscle. We did not observe any transduction of spinal motoneurons following intramuscular injection of AAV vectors. These results show that physiologically and clinically important subpopulations of cells in the neuromuscular system can be selectively transduced by viral vectors.