Journal of Physiology

 Postural physiological hand tremor has a prominent component at ~8 Hz unlike the associated EMG. Consequently, the gain between EMG and tremor is sharply peaked at ~8 Hz.

 Deduction and a simple model using pre-recorded EMG or random noise as an input show that the ~8 Hz peak is a consequence of resonance.

 During voluntary movement the gain peak enlarges and shifts to a lower frequency but the EMG spectrum shows no corresponding changes. This reflects muscle thixotropy. Adjustment of the muscle properties of the model reproduces the effect.

 These findings suggest that the rhythm of hand tremor in posture and movement is related to muscle and limb mechanics rather than a neural oscillator.

 The discovery that the gain relating EMG to acceleration is very different when static and moving has implications for the control of movement in health and disease.

 We provide novel evidence for the effects of metabolic dysfunctions on brain function using the rat model of metabolic syndrome induced by high fructose intake.

 We describe that the deleterious consequences of unhealthy dietary habits can be partially counteracted by dietary supplementation of n-3 fatty acid.

 High sugar consumption impaired cognitive abilities and disrupted insulin signalling by engaging molecules associated with energy metabolism and synaptic plasticity; in turn, the presence of docosahexaenoic acid, an n-3 fatty acid, restored metabolic homeostasis.

 These findings expand the concept of metabolic syndrome affecting the brain and provide the mechanistic evidence of how dietary habits can interact to regulate brain functions, which can further alter lifelong susceptibility to the metabolic disorders.

 In mouse models for retinal degeneration, photoreceptor death leads to membrane oscillation in the remnant AII amacrine–ON cone bipolar cell network through an unknown mechanism.

 We found such oscillations require voltage-gated Na+ channels and gap junctions but not hyperpolarization-activated currents (Ih).

 Na+ channels are expressed predominantly in AII amacrine cells and Ih in ON cone bipolar cells, and appear to interact via gap junctions to shape oscillations.

 Similar intrinsic oscillations arose in the wild-type (wt) AII amacrine–ON cone bipolar cell network when photoreceptor inputs to bipolar cells were pharmacologically occluded.

 Computational modelling captures experimental findings when a low level of cellular heterogeneity is introduced in the coupled network.

 These unique insights into the cellular mechanisms underlying spontaneous activity in the degenerating retina might aid in designing the most effective strategies to restore vision using retinal prosthesis.

 Riluzole is the only drug available against amyotrophic lateral sclerosis (ALS), a fatal disease characterized by death of motor neurones.

 Recently it has been shown to block muscle ACh receptors (AChRs), raising concerns about possible side-effects on neuromuscular transmission in patients.

 In this work we studied the effect of riluzole on the function of muscle AChRs in vitro and on neuromuscular transmission in ALS patients.

 Data indicate that riluzole is apparently safe regarding neuromuscular transmission in patients.

 However, riluzole may affect the function of AChRs expressed in denervated muscle fibres of ALS patients, with biological consequences that remain to be investigated.

 The cerebral ventricles of the vertebrate brain form a series of interconnected chambers through which cerebrospinal fluid flows serving an important role in brain homeostasis and development.

 We introduce the larval zebrafish brain as a model for studying the physiology of the cerebral ventricles.

 The three dimensional form of the zebrafish ventricles was characterized by in vivo confocal microscopy and found to be similar to that of mammals.

 To follow the movement of molecules within ventricles we have a developed a technique using the uncaging of a fluorescent molecule.

 Zebrafish larvae provide a tractable model for studying ventricles and the movement of chemicals across the blood–brain barrier.

 The striatum is the largest nucleus of the basal ganglia, a brain structure crucially involved in motor control. Recent results show that nitric oxide plays an important role in striatal pathophysiology.

 The activity of the striatum is modulated by extrinsic neurotransmitters such as serotonin, produced by specialised neurons located in the brainstem.

 This modulation is exerted through control of striatal interneurons. However, nitric oxide-producing interneurons (NOS interneurons) have been difficult to investigate due to their rarity.

 Using transgenic mice in which NOS interneurons express green fluorescent protein, we found that NOS interneurons are strongly inhibited by serotonin.

 This inhibition is mediated by a specific class of serotonin receptors (5-HT2C) causing an increase in a specific potassium conductance (KCNQ).

 These results cast light on the role of serotonin in the striatum, revealing that it tightly controls the activity of the only neuronal type that releases nitric oxide.

 Learning systems equipped with Hebbian-type associative plasticity are prone to runaway dynamics of synaptic weights and lack mechanisms for synaptic competition; these problems can be resolved by heterosynaptic plasticity: changes at synapses which were not active during the induction.

 We show that in layer 2/3 pyramidal neurons from auditory cortex a purely postsynaptic challenge, intracellular tetanization, can induce heterosynaptic plasticity; similar to visual cortex, plasticity direction depends on initial properties of synapses: inputs with initially low release probability tend to potentiate, while those with initially high release probability tend to depress.

 Induction of heterosynaptic plasticity requires intracellular Ca2+ rise and its maintenance involves presynaptic changes, which depend on the nitric oxide signalling pathway.

 We conclude that heterosynaptic plasticity is a common property of supragranular pyramidal neurons mediating cortico-cortical connections in both auditory and visual cortices; it may serve as a mechanism of synaptic weight normalization and synaptic competition in these cortical regions.

 Symptoms of Parkinson's disease are associated with increased bursting activity in the subthalamic nucleus and substantia nigra zona reticulata (SNR).

 In slices of rat brain, a single electrical stimulus to the STN evokes a complex EPSC and bursts of action potentials in SNR neurons.

 We show that dopamine acts at D2-like receptors to cause marked and reversible inhibition of the complex EPSC.

 Dopamine also inhibited stimulus-evoked bursts of action potentials more than reducing spontaneous firing.

 Inhibition of synaptically generated burst firing by D2 receptor agonists may be a clinically important mechanism in the treatment of Parkinson's disease.

 Neurons can be damaged when tissues are stretched or swollen; while astrocytes can contribute to this process, the mechanosensitive response from neurons is unclear.

 We show here that isolated retinal ganglion cell neurons respond to mechanical strain with a rapid, sustained release of the neurotransmitter ATP.

 The conduit for ATP release was through pannexin hemichannels, with probenicid, carbenoxelone and 10panx inhibiting release.

 Once released, this ATP acts back on the neurons to autostimulate lethal P2X7 receptors, as A438079, AZ 10606120 and zinc reduced currents in whole cell patch clamp recordings.

 Blocking release of ATP through pannexin channels, or activation of P2X7 receptors, might be neuroprotective for stretched or swollen neurons.

 Stretch-dependent release of ATP through neuronal pannexins, combined with the autostimulation of the P2X7 receptors, provides a new pathway by which neuronal activity and health can be altered by mechanical strain independently of glial activity.

 Hippocampal CA1 pyramidal neurons receive dual sensory inputs from the cortex directly through the perforant path (PP) and indirectly through the Schaffer collaterals (SC).

 Direct cortical inputs to CA1 pyramidal neurons through the PP are important for synaptic plasticity and memory formation.

 In this study, we show that long-lasting potentiation of glutamatergic synaptic transmission at SC synapses by pairing of PP–SC inputs was suppressed by pharmacological and genetic inhibition of CB1 receptors.

 Inhibition of the enzyme synthesizing the endocannabinoid 2-arachidonoylglycerol (2-AG) prevented the pairing-induced potentiation, while inhibition of the enzyme hydrolysing 2-AG facilitated the potentiation.

 Our results indicate that 2-AG functions as a signalling mediator tuning synaptic efficacy at the proximal synapses of hippocampal CA1 pyramidal neurons while direct and indirect cortical inputs to the same neurons are spatiotemporally primed, suggesting that endocannabinoids are involved in the information processing and storage in the hippocampus.

 Following release of glutamate from excitatory synapses, excitatory amino acid transporters (EAATs) sequester this glutamate into neighbouring astrocytes.

 The signalling effects on the astrocyte and the mechanisms by which this glutamate is recycled back to the synapse are currently unclear.

 In this study we use electrophysiological recording from neurones and astrocytes to show that a surge of the neurotransmitter glutamate, as usually occurs during neuronal activity, activates astrocytes and causes them to rapidly release the amino acid glutamine.

 This glutamine mediates a fast signal back to the neurones, where it is sequestered and is available for the biosynthesis of further neurotransmitters.

 Our data demonstrate a novel feedback mechanism by which astrocytes can potentially modulate neuronal function, and pave the way for development of new therapeutic approaches to treat neurological disorders.

 Rapid exchange of metabolites like glucose and lactate between different cell types is crucial for energy supply to the brain.

 Carbonic anhydrase 2 (CAII) enhances lactate transport in mouse cerebellar and cerebral astrocytes.

 Enhancement of transport activity is independent of the enzyme's catalytic function, but requires binding of CAII to the C-terminal tail of the monocarboxylate transporter MCT1.

 CAII could enhance lactate flux by acting as a ‘proton collecting antenna' for MCT1.

 By this mechanism CAII could enhance transfer of lactate between astrocytes and neurons and thus provide neurons with an increased supply of energy substrate.

 When photoreceptors in vertebrate retina are exposed to bright light, a significant proportion of the photopigment in the rods can be bleached.

 Bleaching produces a desensitization of the visual system that recovers slowly as pigment is slowly regenerated, by a process known as dark adaptation.

 Experiments on isolated amphibian rods have revealed some of the features of bleach-induced desensitization, but such experiments have not so far been possible on mammals.

 We now describe an improved method that makes possible the first direct measurements of pigment concentration and rod photoreceptor responses over a wide range of bleaching exposures from isolated cells or pieces of intact mammalian retina.

 Our experiments reveal important features of mammalian bleaching adaptation and will now make possible future studies from mouse animal lines containing genetically altered photoreceptor proteins.

 Increases in the strength of synaptic connections in the motor cortex (long term potentiation) can be induced in humans by repetitively pairing peripheral nerve stimuli and motor cortex transcranial magnetic stimuli given 21–25 ms apart – paired associative stimulation (PAS).

 This ‘associative plasticity' effect has been assumed to relate to synchronicity between sensory input and motor output, with a similar mechanism proposed to underlie effects at all interstimulus intervals.

 Here we show that modulation of cerebellar activity using transcranial direct current stimulation can abolish associative plasticity in the motor cortex, but only for sensory/motor stimuli paired at 25 ms, not at 21.5 ms.

 The results indicate that human associative plasticity can be affected by cerebellar activity and that at least two different mechanisms are involved in the effects previously reported in studies using PAS at different inter-stimulus intervals.