A pathway in primate brain for internal monitoring of movements

It is essential to keep track of the movements we make, and one way to do that is to monitor correlates, or corollary discharges, of neuronal movement commands. We hypothesized that a previously identified pathway from brainstem to frontal cortex might carry corollary discharge signals. We found that neuronal activity in this pathway encodes upcoming eye movements and that inactivating the pathway impairs sequential eye movements consistent with loss of corollary discharge without affecting single eye movements. These results identify a pathway in the brain of the primate Macaca mulatta that conveys corollary discharge signals.     

Initiation of behavior by single neurons: the role of behavioral context

Flying crickets avoid sources of ultrasound, possibly echolocating bats, by making rapid steering movements that turn them away from the stimulus. Electrical stimulation of a single, identified sensory interneuron (Int-1) elicits avoidance steering; depressing its response to ultrasound abolishes avoidance steering. Int-1 is necessary and sufficient for this behavior but only while the cricket is in flight. Thus, the sufficiency of Int-1 for eliciting this behavior is contingent on behavioral context.     

Synaptic rearrangement during postembryonic development in the cricket

Synaptic rearrangement during development is a characteristic of the vertebrate nervous system and was thought to distinguish vertebrates from the invertebrates. However, examination of the wind-sensitive cercal sensory system of the cricket demonstrates that some identified synaptic connections systematically decrease in strength as an animal matures, while others increase in strength over the same period. Moreover, a single sensory neuron could increase the strength of its synaptic connection with one interneuron while decreasing the strength of its connection with another interneuron. Thus, rather than being a hallmark of the vertebrate nervous system, synaptic rearrangement is probably characteristic of the development of many if not all nervous systems.     

Functional properties of individual neuronal branches isolated in situ by laser photoinactivation

The functional properties of an isolated dendritic branch of an identified sensory interneuron in the cricket were studied. The branch responded to wind stimuli directed at the animal and displayed a distinct directional sensitivity to those stimuli. A technique was used that allows a neuron to be specifically lesioned in a semi-intact preparation during intracellular recording. Lesioning was achieved by dye-sensitized photoinactivation with a laser epi-illumination stereomicroscope.     

Molecular architecture of the "stressosome," a signal integration and transduction hub

A commonly used strategy by microorganisms to survive multiple stresses involves a signal transduction cascade that increases the expression of stress-responsive genes. Stress signals can be integrated by a multiprotein signaling hub that responds to various signals to effect a single outcome. We obtained a medium-resolution cryo-electron microscopy reconstruction of the 1.8-megadalton "stressosome" from Bacillus subtilis. Fitting known crystal structures of components into this reconstruction gave a pseudoatomic structure, which had a virus capsid-like core with sensory extensions. We suggest that the different sensory extensions respond to different signals, whereas the conserved domains in the core integrate the varied signals. The architecture of the stressosome provides the potential for cooperativity, suggesting that the response could be tuned dependent on the magnitude of chemophysical insult.     

Normalization for sparse encoding of odors by a wide-field interneuron

Sparse coding presents practical advantages for sensory representations and memory storage. In the insect olfactory system, the representation of general odors is dense in the antennal lobes but sparse in the mushroom bodies, only one synapse downstream. In locusts, this transformation relies on the oscillatory structure of antennal lobe output, feed-forward inhibitory circuits, intrinsic properties of mushroom body neurons, and connectivity between antennal lobe and mushroom bodies. Here we show the existence of a normalizing negative-feedback loop within the mushroom body to maintain sparse output over a wide range of input conditions. This loop consists of an identifiable "giant" nonspiking inhibitory interneuron with ubiquitous connectivity and graded release properties.     

A direct synaptic connection mediating both excitation and inhibition

Neurons have generally been thought to produce only one synaptic action on any particular cell which they innervate. An identified interneuron in the abdominal ganglion of Aplysia mediates both direct excitation and inhibition to an identified follower cell. At low firing rates the interneuron produces excitatory postsynaptic potentials; however at higher firing rates these gradually diminish in size and eventually invert to inhibitory postsynaptic potentials. Electrophysiological and pharmacological evidence indicates that the connection between these cells is monosynaptic, and that a single transmitter, acetylcholine, mediates both actions. These opposite synaptic responses appear to result from the transmitter's acting on two types of postsynaptic receptors having different thresholds for activation and different susceptibilities for desensitization.     

Central projections of identified, unmyelinated (C) afferent fibers innervating mammalian skin

Unmyelinated (C) fibers are the most numerous sensory elements of mammalian peripheral nerve and comprise many of those responsible for initiating pain and temperature reactions; however, direct evidence has been lacking as to where and how these fibers terminate in the central nervous system. A plant lectin (Phaseolus vulgaris leukoagglutinin) was applied intracellularly by iontophoresis as an immunocytochemical marker. This permitted visualization of the central terminations of cutaneous C sensory fibers that had been identified by the nature of stimuli that excited them. The central branch of C-fiber units arborized and terminated mainly in the superficial layers of the spinal dorsal horn in defined patterns that related to their functional attributes. Thus, the superficial dorsal horn seems to act as a processing station for signals from fine sensory fibers.     

Opposite synaptic actions mediated by different branches of an identifiable interneuron in Aplysia

Among the identifiable cells in the abdominal ganglion of Aplysia californica are five that generate bursting rhythms endogenous to the cells. In the four bursting cells of the left upper quadrant the rhythm is modulated by a unitary inhibitory postsynaptic potential; in the bursting cell of the right lower quadrant the rhythm is modulated by a unitary excitatory postsynaptic potential. Both the excitatory and inhibitory postsynaptic potentials are mediated by separate branches of a single interneuron. The pharmacological properties of the double action interneuron as well as those of the follower cells suggest that a single transmitter (acetylcholine) is involved in both the excitatory and the in-hibitory action of the interneuron.     

Regeneration electrode units: implants for recording from single peripheral nerve fibers in freely moving animals

Implantable electrode assemblies that become penetrated by regenerating axons were used to record signals from single sensory and motor nerve fibers associated with leg movement in unrestrained amphibians (Xenopus laevis). Such neuroimplants may provide a means for establishing the roles of various muscle afferents and efferents in posture and locomotion, and have potential clinical applications.     

Evidence for brainstem structures participating in oculomotor integration

The cerebellar flocculus has been implicated in vestibulo-oculomotor control. One major central input to this structure originates from brainstem cells in the paramedian tract (PMT), whose function is unknown. Here it is reported that PMT cells in the pons carry vestibular and eye movement signals and their pharmacological inactivation produces a leaky integrator combined with vestibular imbalance. The results suggest that PMT cells provide the cerebellum with sensory and motor signals that are essential for velocity-to-position integration, a common premotor process that is required in all motor systems.     

Glia are essential for sensory organ function in C. elegans

Sensory organs are composed of neurons, which convert environmental stimuli to electrical signals, and glia-like cells, whose functions are not well understood. To decipher glial roles in sensory organs, we ablated the sheath glial cell of the major sensory organ of Caenorhabditis elegans. We found that glia-ablated animals exhibit profound sensory deficits and that glia provide activities that affect neuronal morphology, behavior generation, and neuronal uptake of lipophilic dyes. To understand the molecular bases of these activities, we identified 298 genes whose messenger RNAs are glia-enriched. One gene, fig-1, encodes a labile protein with conserved thrombospondin TSP1 domains. FIG-1 protein functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. Our results suggest that glia are required for multiple aspects of sensory organ function.     

Lateral giant fibers of cray fish: location of somata by dye injection

Using a new technique for injecting fluorescent dye, we have analyzed the intraganglionic architectutre of the lateral giant interneuron in crayfish. Each lateral giant interneuron comprises a giant axon, an ipsilateral dendritic arborization of fairly constant form, and a contralateral soma. Antidromic axon spikes produce only, small, electronic potentials in the soma; direct depolarization there fails to produce electrically excitable membrane responses and cannot discharge the main axon.     

Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices

Attention can be focused volitionally by "top-down" signals derived from task demands and automatically by "bottom-up" signals from salient stimuli. The frontal and parietal cortices are involved, but their neural activity has not been directly compared. Therefore, we recorded from them simultaneously in monkeys. Prefrontal neurons reflected the target location first during top-down attention, whereas parietal neurons signaled it earlier during bottom-up attention. Synchrony between frontal and parietal areas was stronger in lower frequencies during top-down attention and in higher frequencies during bottom-up attention. This result indicates that top-down and bottom-up signals arise from the frontal and sensory cortex, respectively, and different modes of attention may emphasize synchrony at different frequencies.     

Extracellular potassium ions mediate specific neuronal interaction

The giant interneurons from the nerve system of the cockroach Periplaneta americana exhibit a peculiar reciprocal synaptic interaction. The synaptic potentials are not blocked by addition of 5 millimolar cobalt chloride and have an extrapolated reversal potential close to 0 millivolt. Hyperpolarizing current injected into one cell does not spread to the other. Intracellular injection of tetraethylammonium ions into one giant interneuron increases the duration of the action potential of the injected cell to 30 milliseconds and reduces the rise time and amplitude of the postsynaptic response recorded in the other giant interneuron. These results indicate that the interaction between the interneurons is not mediated by conventional chemical or electrotonic synapses.. All evidence points to generation of the potentials by localized increases in extracellular potassium concentrations as a consequence of firing of one neuron.     

Release of coordinated behavior in crayfish by single central neurons

By stimulating and recording from the same interneuron at two separate points, we have shown that coordinated output to the postural abdominal muscles of crayfish can be produced by electrical stimulation of a single cell. Several central neurons can individually initiate one type of movement(for example, flexion),each producing a unique abdominal geometry.     

MHC class I peptides as chemosensory signals in the vomeronasal organ

The mammalian vomeronasal organ detects social information about gender, status, and individuality. The molecular cues carrying this information remain largely unknown. Here, we show that small peptides that serve as ligands for major histocompatibility complex (MHC) class I molecules function also as sensory stimuli for a subset of vomeronasal sensory neurons located in the basal Gao- and V2R receptor-expressing zone of the vomeronasal epithelium. In behaving mice, the same peptides function as individuality signals underlying mate recognition in the context of pregnancy block. MHC peptides constitute a previously unknown family of chemosensory stimuli by which MHC genotypic diversity can influence social behavior.     

Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex

A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.     

Corollary discharge provides accurate eye position information to the oculomotor system

The saccadic system accurately compensates for perturbations of eye position produced by microstimulation of the superior colliculus. This requires that information about the stimulation-induced change in eye position be provided by an extraretinal source--either proprioceptive endings in extraocular muscles or a centrally generated corollary discharge. It is shown that compensation remains intact after elimination of extraocular muscle proprioception, demonstrating that corollary discharge provides accurate eye position information.     

Synaptic activation of an electrogenic sodium pump

An identified molluscan interneuron mediates different cholinergic synaptic actions by increasing the conductance of its follower cells to different ions. We have now found that this interneuron also mediates a new class of synaptic actions which does not involve a conductance change but the activation of an electrogenic sodium pump. This synaptic action results in a prolonged inhibitory synaptic potential which is dependent on metabolism and is selectively blocked by cooling and ouabain. In cells which have this synaptic potential, part of the resting membrane potential is also maintained by an electrogenic sodium pump. The same transmitter, acetylcholine, can independently stimulate both a chloride ion conductance and a sodium pump mechanism in the same follower cell by acting on two different postsynaptic receptors.