Principle of neuronal organization of defensive reflexes in mollusks

Spontaneous and evoked synaptic activity of command neurons for the defensive response of spiracle closing were studied by simultaneous intracellular recording of activity of several identified CNS neurons in snails. Comparison of monosynaptic EPSPs in command neurons evoked by discharges of presynaptic neurons with spontaneous synaptic potentials indicated that the central organization of the defensive reflex is in the form of a two-layered neuron net in which each neuron of the afferent layer possesses a local receptive field, but which overlaps with other afferent neurons. Each neuron of the afferent layer is connected with each neuron of the efferent layer by monosynaptic excitatory connections that differ in efficiency (maximal only with one neuron of the efferent layer). Both receptive fields of neurons of the afferent layer and "fields of efficiency of synaptic connections" are distributed according to the normal law. As a result of this organization the neuron net acquires a new quality: The action of different stimuli leads to the appearance of differently located "spatial excitation profiles" of efferent layer neurons even when this action of the stimulus occurs not at the center of the receptive field.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 26–34, January-February, 1984.     

Generation of grouped discharges by tectal projection cells

In this paper we briefly summarize our recent data on the transduction properties of tecto-bulbo-spinal neurons (TBSN) in the cat. These neurons from an important link between the superior colliculus and the "premotor" structures of the brain stem and the cervical spinal cord. They are closely similar to spinal alpha-motoneurons, as concerns the soma-dendritic geometry and electrotonic parameters. In contrast, their rhythmic firing behavior is characterized by much higher sensitivity to depolarizing currents and by the capability ot generate extraspikes ("regenerative firing mode"). This results in an abrupt increase of sensitivity when a certain limit of depolarization is surpassed. Membrane parameters of TBSN which are responsible for their characteristic transduction properties are presented. We forward an hypothesis that different modes of rhythmic firing, as dependent on behavioral situation, play a role in the distribution of efferent signals among many different target areas of TBSNs.     

Convergence of Signals and Reorganization of Neuronal Activity in a Model of Neuronal Network and in Striatum of the Monkey Brain

To elucidate principles of neuronal organization providing preservation of informational content of converging impulse flows in afferent impulsation of neurons, a comparison is performed of results obtained in the previously carried out experiments on a model of neuronal network and in a study of correlates of behavior in the neuronal network of the monkey brain neostriatum (putamen). This comparison has shown that responses of the neuronal network model to different ratio of input impulse flows and changes of the neostriatal neuronal activity, which accompany different behavioral actions, are seen the most clearly in reorganization of composition of the most active neurons. Each combination of input signals and each behavioral action of the animal correspond to a non-repeated mosaic of neuronal activity. The data obtained indicate that the neuronal network, both real and in the simplest model variant, is able to transform the converging input signals into the mosaic equivalent to their entire combination and thereby to transmit the result of generalization of the input signals of the network to the innervated brain structures.     

Analysis of the neuronal selectivity underlying low fMRI signals

BACKGROUND: A prevailing assumption in neuroimaging studies is that relatively low fMRI signals are due to weak neuronal activation, and, therefore, they are commonly ignored. However, lower fMRI signals may also result from intense activation by highly selective, albeit small, subsets of neurons in the imaged voxel. We report on an approach that could form a basis for resolving this ambiguity imposed by the low (mm range) spatial resolution of fMRI. Our approach employs fMR-adaptation as an indicator for highly active neuronal populations even when the measured fMRI signal is low.RESULTS: In this study, we first showed that fMRI-adaptation is diminished when overall neuronal activity is lowered substantially by reducing image contrast. We then applied the same adaptation paradigm, but this time we lowered the fMRI signal by changing object shape. While the overall fMRI signal in category-related regions such as the face-related pFs was drastically reduced for non-face stimuli, the adaptation level obtained for these stimuli remained high. We hypothesize that the relatively greater adaptation level following exposure to "nonoptimal" object shapes is indicative of small subsets of neurons responding vigorously to these "nonoptimal" objects even when the overall fMRI activity is low.CONCLUSIONS: Our results show that fMR-adaptation can be used to differentiate between neuronal activation patterns that appear similar in the overall fMRI signal. The results suggest that it may be possible to employ fMR-adaptation to reveal functionally heterogeneous islands of activity, which are too small to image using conventional imaging methods.     

Morphology and central synaptic connections of the efferent neurons innervating the crayfish hindgut

Summary The distribution, morphology and synaptic connections of the hindgut efferent neurons in the last (sixth) abdominal ganglion of the crayfish, Orconectes limosus, have been investigated using light and electron microscopy in conjunction with retrograde cobalt/nickel and HRP labeling through the intestinal nerve. The hindgut efferent neurons occur singly and in clusters, and are unipolar. Their axonal projections are uniform and consist of a thick primary neurite with typical lateral projections and limited arborization of varicose fibers in the ganglionic neuropil. They also send lower order axon processes to the ganglionic neural sheath, where they arborize profusely, forming a network of varicose fibers. The majority of the efferent neurons project to the anterior part of the hindgut. HRP-labeled axon profiles are found in both pre- and postsynaptic position in the neuropil of the ganglion. HRP-labeled axon profiles also establish pre- and postsynaptic contacts in the intestinal nerve root. All hindgut efferent terminals contain similar synaptic vesicle populations: ovoid agranular vesicles (50–60 nm) and a few large granular vesicles (100–200 nm). It is suggested that the hindgut efferent neurons in the last abdominal ganglion are involved in: (1) innervation of the hindgut; (2) central integrative processes; (3) en route synaptic modification of efferent and afferent signals in the intestinal nerve; (4) neurohumoral modulation of peripheral physiological processes.Fellow of the Alexander von Humboldt Stiftung     

Neuron death in the developing avian isthmo-optic nucleus, and its relation to the establishment of functional circuitry.

The present review covers all the published data on neuron death in the developing avian isthmo-optic nucleus (ION), which provides a particularly convenient situation for studying the causes and consequences of neuron death in the development of the vertebrate central nervous system. The main conclusions are as follows: The naturally occurring neuron death in the ION is related both temporally and causally to the ION's formation of afferent and efferent connections. The ION neurons need to obtain both anterograde and retrograde survival signals in order to survive during a critical period in embryogenesis. They may compete, at least for the retrograde signals, but the nature of the competition is still unclear. The retrograde signals are modified by action potentials. Neurons dying from a lack of anterograde survival signals can be distinguished morphologically from ones dying from a lack of retrograde signals. The neuron death refines circuitry by selectively eliminating neurons with "aberrant" axons projecting to the "wrong" (i.e., ipsilateral) retina or to the "wrong" (topographically inappropriate) part of the contralateral retina.     

Populations of behavior-reactive neurons in the monkey neostriatum

Comparative analysis of the unit activity of the monkey putamen during multistage behavior showed that neurons of the putamen are active during all the behavioral actions. It was established that the number of the behavior-related neurons changes considerably less than number of neurons which reorganize their activity at the time. Reorganization of unit activity in the putamen is considered as reflecting the efferent code which controls behavior, and the degree of reorganization--as a measure of change of this code in relation to organization of ongoing behavioral action. It has been discovered that the change in the number of the active neurons at various steps of behavior and reorganization of their activity occurs independently. It may be related to two main afferent systems of striatum: ascending from rhe brain stem, and corticofugal which brings differentiated information to the neuronal net of striatum from various parts of the cortex.     

Neural simulations of adaptive reafference suppression in the elasmobranch electrosensory system

The electrosensory system of elasmobranchs is extremely sensitive to weak electric fields, with behavioral thresholds having been reported at voltage gradients as low as 5 nV/cm. To achieve this amazing sensitivity, the electrosensory system must extract weak extrinsic signals from a relatively large reafferent background signal associated with the animal's own movements. Ventilatory movements, in particular, strongly modulate the firing rates of primary electrosensory afferent nerve fibers, but this modulation is greatly suppressed in the medullary electrosensory processing nucleus, the dorsal octavolateral nucleus. Experimental evidence suggests that the neural basis of reafference suppression involves a common-mode rejection mechanism supplemented by an adaptive filter that fine tunes the cancellation. We present a neural model and computer simulation results that support the hypothesis that the adaptive component may involve an anti-Hebbian form of synaptic plasticity at molecular layer synapses onto ascending efferent neurons, the principal output neurons of the nucleus. Parallel fibers in the molecular layer carry a wealth of proprioceptive, efference copy, and sensory signals related to the animal's own movements. The proposed adaptive mechanism acts by canceling out components of the electrosensory input signal that are consistently correlated with these internal reference signals.Abbreviations AEN ascending efferent neuron - AFF primary afferent nerve fiber - DGR dorsal granular ridge - DON dorsal octavolateral nucleus - ELL electrosensory lateral line lobe - GABA -aminobutyric acid - IN inhibitory interneuron - ISI interspike interval - ST stellate cell     

Cardiac neuronal hierarchy in health and disease

The cardiac neuronal hierarchy can be represented as a redundant control system made up of spatially distributed cell stations comprising afferent, efferent, and interconnecting neurons. Its peripheral and central neurons are in constant communication with one another such that, for the most part, it behaves as a stochastic control system. Neurons distributed throughout this hierarchy interconnect via specific linkages such that each neuronal cell station is involved in temporally dependent cardio-cardiac reflexes that control overlapping, spatially organized cardiac regions. Its function depends primarily, but not exclusively, on inputs arising from afferent neurons transducing the cardiovascular milieu to directly or indirectly (via interconnecting neurons) modify cardiac motor neurons coordinating regional cardiac behavior. As the function of the whole is greater than that of its individual parts, stable cardiac control occurs most of the time in the absence of direct cause and effect. During altered cardiac status, its redundancy normally represents a stabilizing feature. However, in the presence of regional myocardial ischemia, components within the intrinsic cardiac nervous system undergo pathological change. That, along with any consequent remodeling of the cardiac neuronal hierarchy, alters its spatially and temporally organized reflexes such that populations of neurons, acting in isolation, may destabilize efferent neuronal control of regional cardiac electrical and/or mechanical events.     

High vocal center growth and its relation to neurogenesis,neuronal replacement and song acquisition in juvenile canaries

It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brainassembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43%–0.64% of the HVC neurons present at 1 year of age are labeled per day of [³H]-thymidine injection. [³H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning.     

High vocal center growth and its relation to neurogenesis, neuronal replacement and song acquisition in juvenile canaries.

It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brain assembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43%-0.64% of the HVC neurons present at 1 year of age are labeled per day of [3H]-thymidine injection. [3H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning.     

A combined Bodian-Nissl stain for improved network analysis in neuronal cell culture

Bodian and Nissl procedures were combined to stain dissociated mouse spinal cord cells cultured on coverslips. The Bodian technique stains fine neuronal processes in great detail as well as an intracellular fibrillar network concentrated around the nucleus and in proximal neurites. The Nissl stain clearly delimits neuronal cytoplasm in somata and in large dendrites. A combination of these techniques allows the simultaneous depiction of neuronal perikarya and all afferent and efferent processes. Costaining with little background staining by either procedure suggests high specificity for neurons. This procedure could be exploited for routine network analysis of cultured neurons.     

Maintaining the neuronal phenotype after injury in the adult CNS

Multiple genetic and epigenetic events determine neuronal phenotype during nervous system development. After the mature mammalian neuronal phenotype has been determined it is usually static for the remainder of life, unless an injury or degenerative event occurs. Injured neurons may suffer one of three potential fates: death, persistent atrophy, or recovery. The ability of an injured adult neuron to recover from injury in adulthood may be determined by events that also influence neuronal phenotype during development, including expression of growth-related genes and responsiveness to survival and growth signals in the environment. The latter signals include neurotrophic factors and substrate molecules that promote neurite growth. Several adult CNS regions exhibit neurotrophic-factor responsiveness, including the basal forebrain, entorhinal cortex, hippocampus, thalamus, brainstem, and spinal cord. The specificity of neurotrophic-factor responsiveness in these regions parallels patterns observed during development. In addition, neurons of several CNS regions extend neurites after injury when presented with growth-promoting substrates. Whenboth neurotrophic factors and growth-promoting substrates are provided to adult rats that have undergone bilateral fimbria-fornix lesions, then partial morphological and behavioral recovery can be induced. Gene therapy is one useful tool for providing these substances. Thus, the mature CNS remains robustly responsive to signals that shape nervous system development, and is highly plastic when stimulated by appropriate cues.     

Midline lineages in grasshopper produce neuronal siblings with asymmetric expression of Engrailed

The median neuroblast lineage of grasshopper has provided a model for the development of differing neuronal types within the insect central nervous system. According to the prevailing model, neurons of different types are produced in sequence. Contrary to this, we show that each ganglion mother cell from the median neuroblast produces two neurons of asymmetric type: one is Engrailed positive (of interneuronal fate); and one is Engrailed negative (of efferent fate). The mature neuronal population, however, results from differential neuronal death. This yields many interneurons and relatively few efferent neurons. Also contrary to previous reports, we find no evidence for glial production by the median neuroblast. We discuss evidence that neuronal lineages typically produce asymmetric progeny, an outcome that has important developmental and evolutionary implications.     

Paradoxical REM sleep promoting and permitting neuronal networks

Since its electrophysiological identification in the 1950's, the state of REMS or PS has been shown through multiple lines of evidence to be generated by neurons in the oral pontine tegmentum. The perpetration of this paradoxical state that combines cortical activation with the most profound behavioral sleep occurs through interplay between PS-promoting (On) and PS-permitting (Off) cell groups in the pons. Cholinergic cells in the LDTg and PPTg promote PS by initiating processes of both forebrain activation and peripheral muscle atonia. Bearing alpha1-adrenergic receptors, cholinergic cells, which likely project to the forebrain, are excited by NA and active during both W and PS (W/PS-On), when they promote cortical activation. Bearing alpha2-adrenergic receptors, other cholinergic cells, which likely project to the brainstem, are inhibited by NA and thus active selectively during PS (PS-On), when they promote muscle atonia. Noradrenergic, together with serotonergic, neurons, as PS-Off neurons, thus permit PS in part by lifting their inhibition upon the cholinergic PS-On cells. The noradrenergic/serotonergic neurons are inhibited in turn by local GABAergic PS-promoting neurons that may be excited by ACh. Other similarly modulated GABAergic neurons located through the brainstem reticular formation become active to participate in the inhibition of reticulo-spinal and raphe-spinal neurons as well as in the direct inhibition of motor neurons. In contrast, a select group of GABAergic neurons located in the oral pontine reticular formation and possibly inhibited by ACh turn off during PS. These GABAergic PS-permitting neurons release from inhibition the neighboring large glutamatergic neurons of the oral pontine reticular formation, which are likely concomitantly excited by ACh. In tandem with the cholinergic neurons, these glutamatergic reticular neurons propagate the paradoxical forebrain activation and peripheral inactivation that characterize PS.     

Timing of neural commands: a model study with neuronal networks

Networks constructed of biologically realistic model neurons (neuroids) were used to study how in a neural assembly using pulse (interval)-coded information slow rhythmical oscillations with possible mode transitions might occur and how the efferent commands might be structured and their phase-shifts created. The simulations show that slow oscillations (in the hertz range) can be derived from reverberatory spiking in relatively short closed loops (fewer than ten neuroids) with the inputs protected against disturbing afferent signals and the outputs coupled by convergence on a common neuroid. Slow oscillations can be modified by a tonic activity entering the network; this activity changes the transmission time in the coupled loops involved. The structuring of the regulatory commands (in the millisecond range) was achieved by simulation of sequential activity propagation in a non-ring neuronal assembly supervised by a tonic activity in a set of inputs. The tonic activity acted as an instructive signal influencing the pattern of the functional connectivity in such a way that a particular efferent command was generated by the instructed network. Received: 3 March 1997 / Accepted in revised form: 15 July 1997     

The neuronal primary cilium--an extrasynaptic signaling device

Many, but likely most, neurons in the central nervous system have a nonmotile "primary" cilium extending like an antenna or finger from one of the pair of centrioles in the cell's centrosome into the extracellular space. Since their discovery over 100 years ago, these organelles have been either dismissed as functionless relicts of a bygone era or more often simply ignored. However, it has long been known that the photoreceptor-bearing outer segments of retinal rods and cones are modified primary cilia and it has recently been found that kidney cells' primary cilia are sensitive flowmeters the disabling of which causes polycystic kidney disease. It has also been recently shown that somatostatin sst3 receptors and serotonin 5-HT(6) receptors are selectively sited on neurons in various parts of the rat brain. It seems likely that these selectively receptored neuronal primary cilia will turn out to be the forerunners of a family of cell-signaling devices that help drive various brain functions by sending signals into their own cells and into adjacent cells through gap junctions and via conventional chemical synapses.     

Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential <−75 mV and their passive responses in the hyperpolarizing range. In contrast, the response properties of VE and LOC neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs.     

Decision-making in the leech nervous system

Previous models of behavioral choice have described two types of hierarchy, a decision hierarchy, in which different classes of decisions are made at each level (Tinbergen, 1951), and a behavioral hierarchy, in which one behavior will take precedence over others (Davis, 1985). Most experimental work on the neuronal basis of decision-making has focussed on the latter of these: a behavioral hierarchy is described for an animal, and the neuronal basis for this hierarchy, hypothesized to depend on inhibitory interactions, is investigated. Although the concept of "dedicated command neurons" has been useful for guiding these studies, it appears that such neurons are rare. We present evidence that in the leech, most neurons, including high-level decision neurons, are active in more than one behavior. We include data from one newly-identified neuron that elicits both swimming and crawling motor patterns. We suggest that decisions are made by a "combinatorial code": what behavior is produced depends on the specific combination of decision neurons that are active at a particular time. Finally, we discuss how decision neurons may be arranged into a decision hierarchy, with neurons at each sequential level responsible for choosing between a narrower range of behaviors. We suggest additional sensory information is incorporated at each level to inform the decision.