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Functional connections between neurons of interpositus nucleus of the cerebellum and the red nucleus.

Patterns of functional connections between individual neurons of nucleus interpositus (IP) of the cerebellum and red nucleus (RN) were examined. This was assessed by cross-correlation of spike trains characterizing interaction between simultaneously recorded neurons. Direct interpositorubral connections were always excitatory in nature: direct inhibition was only found within and not between these nuclei. Shared inputs from common sources outnumber other types of interpositorubral connections. Patterns of connection between IP RN neurons could be influenced by sensorimotor cortex.

Afferent Pathways↗

[A hypothalamic hormone-somatostatin--from endocrinology to neurophysiology].

The densest distribution of somatostatin (SRIF) neuron perikarya is localized in the hypothalamic periventricular nucleus (Pe) close to the third ventricle, from which many fibers are projected to the median eminence. The release of SRIF in the neurohemal organ into the anterior pituitary modulates GH secretion from pituitary somatotrophs. When SRIF input from the hypothalamus to rat anterior pituitary is reduced by either neurosurgery or SRIF antiserum iv injection, the responsiveness of the pituitaries to human GH releasing factor (hGRF) in an in vitro perifusion system is markedly attenuated. Moreover, SRIF pretreatment facilitates the GH release response of dispersed anterior pituitary cells to hGRF. The long lasting SRIF effect to sensitize somatotrophs appears to take place beyond cAMP formation or as an unknown distal effect. These findings indicate that SRIF neurons in the Pe play a role in maintaining the pituitary responsiveness to GRF in addition to the original action to inhibit GH secretion. Neuronal networks between Pe-SRIF neurons, and intra- and extrahypothalamic nuclei are identified by Pe stimulation test on GRF-GH secretion. In addition to the physiological role in maintaining pituitary responsiveness, Pe SRIF neurons have a wide influence on specific SRIF receptor binding in various brain regions as well as in the anterior pituitary. Shortly after lesioning the Pe neurons, there is a continuous increase in plasma GH level with a transient increase in specific binding of 125I-Tyr 11-SRIF-14 to the anterior pituitary. Furthermore, there is a similar but a little longer increase in binding of the radioligand to some brain areas such as the cerebral cortex, hippocampus, and amygdala nuclei. However, neuronal connections between the SRIF neurons and nuclei which are up-regulated by the lesioning have not been fully proven. When the labeled ligand is infused into the lateral ventricle, it is rapidly and widely distributed in many periventricular structures in the lateral and third ventricles. These findings suggest that SRIF produced in the Pe neurons is transported to other brain areas via cerebrospinal fluid in addition to neuronal connections for modulating the activity of neurons which have SRIF receptors. Thus, hypothalamic Pe SRIF neurons have dualistic roles for controlling anterior pituitary function and modulating CNS neuron activity.

Animals↗

Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46).

An understanding of the normal organization of prefrontal cortex is essential to the recognition of pathology underlying human behavioral disorders believed to depend on this region. We have therefore studied the pattern of intrinsic intra- and interlaminar pyramidal neuron connectivity in prefrontal areas 9 and 46 (of Walker) in macaque monkey cerebral cortex (anterior to the arcuate sulcus between the principal sulcus and midline). We made focal (200-400 microns) injections of biocytin and mapped the pattern of orthogradely transported label. Injections made into the superficial layers label wide-ranging lateral projections within the same areas of prefrontal cortex. Projections local to such small injections form a narrow band of terminals in layers 1-3 (200-400 microns wide, 2-4 mm long) centered on the injection site. Collateral fibers spread orthogonal to this terminal band, making frequent bifurcations, to establish a series of parallel bands of terminals with uninnervated bands between, spaced regularly across the cortex (center to center 500-600 microns). The entire pattern of terminal label is stripe-like, with occasional narrower interbands and crosslinks between the bands, and can extend over 7-8 mm across the cortex. These projections arise from pyramidal neurons in layers 2, 3, and 5 and terminate in layers 1-3. The stripe-like pattern contrasts with patch-like patterns in other cortical regions (V1, V2, V4, motor, somatosensory) and is smaller in scale than stripe-like zones of corticocortical afferent terminals to this region, reported to be 300-750 microns wide and spaced 1.0-1.5 mm center to center.

Animals↗

Neuronal group connecting the nucleus retroambiguus with nucleus ambiguus.

The nucleus retroambiguus is connected to the ambiguus rostrally to the crossing pyramidal fibers and laterally to the crossing lemnisces. The lateral reticular nucleus is positioned laterally and ventrally to the neurons of the connection. The neurons belonging to the connection are medium-sized. Their long dendrites are directed mainly medially, dorsally and ventrally. Medially directed dendrites ascend into the central nucleus of the medulla oblongata. Fibers of the lateral vestibulobulbospinal tract pass through the area of the connection. The tracts of the corticobulbar and medial reticular formations are found in the vicinity of the neuronal group described above. It is not impossible, however, that other, as yet unknown, tracts also pass in the neighbourhood.

Animals↗

Exact solution for the optimal neuronal layout problem.

Evolution perfected brain design by maximizing its functionality while minimizing costs associated with building and maintaining it. Assumption that brain functionality is specified by neuronal connectivity, implemented by costly biological wiring, leads to the following optimal design problem. For a given neuronal connectivity, find a spatial layout of neurons that minimizes the wiring cost. Unfortunately, this problem is difficult to solve because the number of possible layouts is often astronomically large. We argue that the wiring cost may scale as wire length squared, reducing the optimal layout problem to a constrained minimization of a quadratic form. For biologically plausible constraints, this problem has exact analytical solutions, which give reasonable approximations to actual layouts in the brain. These solutions make the inverse problem of inferring neuronal connectivity from neuronal layout more tractable.

Animals↗

A review on electron microscopy and neurotransmitter systems.

The purpose of this article is to review the contributions of transmission electron microscopy studies to the understanding of brain circuits and neurotransmitter systems. Our views on the microstructure of connections between neurons have gradually changed, and now we recognize that the classical mental image we had on a chemical synapse is no longer applicable to every neuronal connection. We highlight studies that converge to point out that, while the most prevalent fast transmitters in the brain, glutamate and GABA, are stored in small, clear synaptic vesicles (SSV) and released at synapses, neuropeptides are exclusively stored in large dense core vesicles (LDCV) and released extrasynaptically. Amine transmitters are preferentially, but not exclusively, accumulated in LDCV and may be released at synaptic or extrasynaptic sites. We discuss evidence suggesting that axon terminals from pyramidal cortical neurons and dorsal thalamic neurons lack LDCV and therefore could not use neuropeptides as transmitters. This idea fits with the fast, high temporal resolution information processing that characterizes cortical and thalamic function.

Animals↗

[Cellular and molecular mechanisms of memory].

There has been nearly a century of interest in the idea that information is encoded in the brain as specific spatio-temporal patterns of activity in distributed networks and stored as changes in the efficacy of synaptic connections on neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular bases of learning and memory. To date, the key events in the cellular and molecular mechanisms underlying synaptic plasticity are starting to be identified. They require the activation of specific receptors and of several molecular cascades to convert extracellular signals into persistent functional changes in neuronal connectivity. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. The recent developments in the search for the cellular and molecular mechanisms of memory storage are reviewed.

Gene Expression Regulation↗

Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column.

Whole-cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/- 0.13. Both c.v. and percentage of failures decreased with increased average EPSP amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At -60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1-100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame synaptic depression so that the summed EPSP was larger than the first EPSP amplitude in the train. The number of putative synaptic contacts established by the axonal collaterals of the L4 projection neurone with the target neurone in layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs). Synapses were established on basal dendrites of the pyramidal cell. Their mean geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16-196 microm). The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in the pyramidal cell. Therefore transmission of signals to layer 2/3 is likely to have a high threshold requiring simultaneous activation of many L4 neurons, implying that L4 spiny neurone to L2/3 pyramidal cell synapses act as a gate for the lateral spread of excitation in layer 2/3.

Action Potentials↗

Chemical implementation of finite-state machines.

With methods developed in a prior article on the chemical kinetic implementation of a McCulloch-Pitts neuron, connections among neurons, logic gates, and a clocking mechanism, we construct examples of clocked finite-state machines. These machines include a binary decoder, a binary adder, and a stack memory. An example of the operation of the binary adder is given, and the chemical concentrations corresponding to the state of each chemical neuron are followed in time. Using these methods, we can, in principle, construct a universal Turing machine, and these chemical networks inherit the halting problem

Journal Article↗

Segregation of the brain into gray and white matter: a design minimizing conduction delays.

A ubiquitous feature of the vertebrate anatomy is the segregation of the brain into white and gray matter. Assuming that evolution maximized brain functionality, what is the reason for such segregation? To answer this question, we posit that brain functionality requires high interconnectivity and short conduction delays. Based on this assumption we searched for the optimal brain architecture by comparing different candidate designs. We found that the optimal design depends on the number of neurons, interneuronal connectivity, and axon diameter. In particular, the requirement to connect neurons with many fast axons drives the segregation of the brain into white and gray matter. These results provide a possible explanation for the structure of various regions of the vertebrate brain, such as the mammalian neocortex and neostriatum, the avian telencephalon, and the spinal cord.

Animals↗

[The vertebrate nervous system comprises an enormous number of cell types].

Neurogenesis is regulated by basic-helix-loop-helix (bHLH) transcription factors in both vertebrates and insects. MASH1 and neurogenin, members of the bHLH genes, are expressed in subsets of neural precursors and control their differentiation. Downstream of the bHLH genes, PHD1, Phox2, and DRG11, which belong to PHD family genes, are expressed in specific lineages of neurons and are involved in their neuronal identity. Differentiated sensory and motor neurons express PEA3 and ER81, members, of the ETS family, which specify neuronal connectivity. During neuronal differentiation, these three families of transcription factors control developmentally distinct operations. Increasing the numbers of members of the families may underlie the generation of neuronal diversity.

Animals↗

Appearance of functional connections between neurons resulting from changes in the frequency of their spike activity during the performance by animals of conditioned-reflex food-procuring responses.

Cats were conditioned to a food-procuring reflex to time. Correlation analysis was applied to multineuron activity in the motor cortex to study the functional connections between neurons with changing and constant instantaneous spike frequencies on performance by the animals of the passive waiting phase of the conditioned reflex, the number of functional connections between "areactive" neurons was smaller than that between "reactive" neurons; during the phase of active waiting, the numbers of functional connections become similar. The increase in the number of functional connections between "areactive" neurons during the active waiting phase appears to reflect an intensification of the analysis and processing of information, while changes in the functional connections between "reactive" neurons was regarded as allowing the possibility of correcting functional structures in the case of a rapid change in the situation or state of the animal.

Action Potentials↗

Ultrastructure and acetylcholinesterase content of neurones forming connections between the striatum and substantia nigra of rat.

Neurones in the striatum and substantia nigra (zona compacta) of the rat were divided into several classes according to differences in morphological appearance and ultrastructural localization of acetylcholinesterase (AChE). To determine which of the neurone types form connections between the substantia nigra and striatum, the ultrastructural localization of AChE was combined with retrograde axonal transport of horseradish peroxidase (HRP). The products of the histochemical reactions for HRP and AChE are localized in separate intracellular compartments and so identification of the efferent cell types was possible. In the striatum there are two morphological classes of AChE-containing neurone and two or three varieties of cell which do not stain for the enzyme. Only one neurone type projects to the substantia nigra and this is a cell with no AChE which makes up 96% of the total neurone population. In the substantia nigra there are two types of neurone with AChE: a cell with rather variable amounts of AChE which projects to the striatum, and another rarer type, possibly an interneurone.

Acetylcholinesterase↗

Regional differences in NREM sleep slow-wave activity in mice with congenital callosal dysgenesis.

Topographic differences in the sleep EEG have been repeatedly found in humans and rodents. A frontal predominance of EEG slow-wave activity (0.75-4 Hz; delta band) during non-rapid eye movement (NREM) sleep is particularly evident under conditions of increased sleep propensity. Local aspects of neuronal connectivity in the neocortex that are modified by specific neuronal stimulation may underlie these differences. To investigate the role of altered neuronal connectivity on anterior-posterior EEG topography, sleep was recorded in mice with congenital dysgenesis of the corpus callosum (B1 strain) during baseline and after 6 h sleep deprivation (SD). In these mice neuronal connections within a hemisphere are increased due to the longitudinal Probst bundle, a structure of re-routed callosal fibers. After SD the frequencies above 1.5 Hz within the delta band in NREM sleep were reduced in B1 mice compared with control C57BL/6 mice, a strain that has a normal corpus callosum, while power in the lowest frequency band (0.75-1.0 Hz) was enhanced in B1 mice. The differences between the strains subsided in the course of recovery. The redistribution of EEG power within the delta band in the frontal region in mice with a well developed Probst bundle, suggests a role of intracortical connectivity in local sleep regulation.

Agenesis of Corpus Callosum↗

The elusive concept of brain connectivity.

Neurons and neural populations do not function as islands onto themselves. Rather, they interact with other such elements through their afferent and efferent connections in an orchestrated manner so as to enable different sensorimotor and cognitive tasks to be performed. The concept of functional connectivity and the allied notion of effective connectivity were introduced to designate the functional strengths of such interactions. Functional neuroimaging methods, especially PET and fMRI, have been used extensively to evaluate the functional connectivity between different brain regions. After providing a brief historical review of these notions of brain connectivity, I argue that the conceptual formulations of functional and effective connectivity are far from clear. Specifically, the terms functional and effective connectivity are applied to quantities computed on types of functional imaging data (e.g., PET, fMRI, EEG) that vary in spatial, temporal, and other features, using different definitions (even for data of the same modality) and employing different computational algorithms. Until it is understood what each definition means in terms of an underlying neural substrate, comparisons of functional and/or effective connectivity across studies may appear inconsistent and should be performed with great caution.

Brain↗

Connectional topography in the zebrafish olfactory system: random positions but regular spacing of sensory neurons projecting to an individual glomerulus.

It is unknown how neuronal connections are specified in the olfactory system. To define rules of connectivity in this system, we investigated whether the projection of sensory neurons from the olfactory epithelium to the olfactory bulb is topographically ordered. By backtracking with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), we find that neurons projecting into a single identified glomerulus are widely dispersed over the olfactory epithelium. Their positions in the sensory surface do not predict their glomerulus specificity and are probably random. A statistical analysis reveals that neurons connected to the same glomerulus are spaced at distances of several cell diameters from each other. The convergence of projections to one point in the target area from neurons that are widely and evenly distributed in the sensory surface constitutes an unusual type of connectional topography that contrasts with the precise topological (neighborhood-preserving) maps found in other sensory systems. It may maximize the probability to detect odorants that activate a single glomerular unit.

Animals↗

Dynamics and pathology of dendritic spines.

Dendritic spines are key players in information processing in the brain. Changes in spine shape and wholesale spine turnover provide mechanisms for modifying existing synaptic connections and altering neuronal connectivity. Although neuronal cell death in acute and chronic neurodegenerative diseases is clearly an important factor in decline of cognitive or motor function, loss of dendritic spines, in the absence of cell death, may also contribute to impaired brain function in these diseases, as well as in psychiatric disorders and aging. Because spines can function in neuroprotection in vitro, advances toward a molecular understanding of spine maintenance might one day aid in the design of therapies to minimize neurological damage following excitotoxic injury. In addition, progress in defining the biochemical basis of spine development and stabilization may yield insights into mental retardation and psychiatric disorders.

Animals↗