Early Development of the Thalamo-Pallial Stage of the Tectofugal Visual Pathway in the Chicken (Gallus gallus).

The tectofugal pathway is a highly conserved visual pathway in all amniotes. In birds and mammals, retinorecipient neurons located in the midbrain roof (optic tectum/superior colliculus) are the source of ascending projections to thalamic relays (nucleus rotundus/caudal pulvinar), which in turn project to specific pallial regions (visual dorsal ventricular ridge [vDVR]/temporal cortex) organized according to a columnar recurrent arrangement of interlaminar circuits. Whether or to which extent these striking hodological correspondences arise from comparable developmental processes is at present an open question, mainly due to the scarcity of data about the ontogeny of the avian tectofugal system. Most of the previous developmental studies of this system in birds have focused on the establishment of the retino-tecto-thalamic connectivity, overlooking the development of the thalamo-pallial-intrapallial circuit. In this work, we studied the latter in chicken embryos by means of immunohistochemical assays and precise ex vivo crystalline injections of biocytin and DiI. We found that the layered organization of the vDVR as well as the system of homotopic reciprocal connections between vDVR layers were present as early as E8. A highly organized thalamo-vDVR projection was also present at this stage. Our immunohistochemical assays suggest that both systems of projections emerge simultaneously even earlier. Combined with previous findings, these results reveal that, in striking contrast with mammals, the peripheral and central stages of the avian tectofugal pathway develop along different timelines, with a tecto-thalamo-intrapallial organization arising before and possibly independently of the retino-isthmo-tectal circuit.

Envelope Analysis of the Human Alpha Rhythm Reveals EEG Gaussianity.

OBJECTIVE: To assess the Gaussianity of the human alpha rhythm using the envelope signal and the coefficient of variation of the envelope (CVE). METHODS: Envelope analysis relies on the fact that the CVE for Gaussian noise is √{(4-π)/π} ≈ 0.523. CVE can thus be used as a hallmark to detect Gaussianity, and any significant deviation from Gaussianity can be linked to synchronous neural dynamics. We applied envelope analysis to EEG and iEEG public databases. RESULTS: The human alpha rhythm can be characterized either as a synchronous or as a Gaussian signal based on the value of its CVE. Furthermore, Fourier analysis showed the canonical spectral peak at ≈ 10[Hz] is present in both the synchronous and Gaussian cases, thus demonstrating this same peak can be produced by different underlying neural dynamics. CONCLUSION: Human EEG can be classified using envelope parameters. This study confirms the original interpretation of Adrian regarding the origin of the alpha rhythm but also opens the door for the study of Gaussianity in brain dynamics. SIGNIFICANCE: Envelope analysis constitutes a novel complement to Fourier-based methods for neural signal analysis relating amplitude modulations (CVE) to signal energy. These results suggest a broader interpretation for event-related synchronization/desynchronization (ERS/ERD) may be needed.

A blinking focal pattern of re-entrant activity in the avian tectum.

Re-entrant connections are inherent to nervous system organization; however, a comprehensive understanding of their operation is still lacking. In birds, topographically organized re-entrant signals, carried by axons from the nucleus-isthmi-parvocellularis (Ipc), are distinctly recorded as bursting discharges across the optic tectum (TeO). Here, we used up to 48 microelectrodes regularly spaced on the superficial tectal layers of anesthetized pigeons to characterize the spatial-temporal pattern of this axonal re-entrant activity in response to different visual stimulation. We found that a brief luminous spot triggered repetitive waves of bursting discharges that, appearing from initial sources, propagated horizontally to areas representing up to 28° of visual space, widely exceeding the area activated by the retinal fibers. In response to visual motion, successive burst waves started along and around the stimulated tectal path, tracking the stimulus in discontinuous steps. When two stimuli were presented, the burst-wave sources alternated between the activated tectal loci, as if only one source could be active at any given time. Because these re-entrant signals boost the retinal input to higher visual areas, their peculiar dynamics mimic a blinking "spotlight," similar to the internal searching mechanism classically used to explain spatial attention. Tectal re-entry from Ipc is thus highly structured and intrinsically discontinuous, and higher tectofugal areas, which lack retinotopic organization, will thus receive incoming visual activity in a sequential and piecemeal fashion. We anticipate that analogous re-entrant patterns, perhaps hidden in less bi-dimensionally organized topographies, may organize the flow of neural activity in other parts of the brain as well.

Envelope analysis links oscillatory and arrhythmic EEG activities to two types of neuronal synchronization.

Traditionally, EEG is understood as originating from the synchronous activation of neuronal populations that generate rhythmic oscillations in specific frequency bands. Recently, new neuronal dynamics regimes have been identified (e.g. neuronal avalanches) characterized by irregular or arrhythmic activity. In addition, it is starting to be acknowledged that broadband properties of EEG spectrum (following a 1/f law) are tightly linked to brain function. Nevertheless, there is still no theoretical framework accommodating the coexistence of these two EEG phenomenologies: rhythmic/narrowband and arrhythmic/broadband. To address this problem, we present a new framework for EEG analysis based on the relation between the Gaussianity and the envelope of a given signal. EEG Gaussianity is a relevant assessment because if EEG emerges from the superposition of uncorrelated sources, it should exhibit properties of a Gaussian process, otherwise, as in the case of neural synchronization, deviations from Gaussianity should be observed. We use analytical results demonstrating that the coefficient of variation of the envelope (CVE) of Gaussian noise (or any of its filtered sub-bands) is the constant 4π-1≈0.523, thus enabling CVE to be a useful metric to assess EEG Gaussianity. Furthermore, a new and highly informative analysis space (envelope characterization space) is generated by combining the CVE and the envelope average amplitude. We use this space to analyze rat EEG recordings during sleep-wake cycles. Our results show that delta, theta and sigma bands approach Gaussianity at the lowest EEG amplitudes while exhibiting significant deviations at high EEG amplitudes. Deviations to low-CVE appeared prominently during REM sleep, associated with theta rhythm, a regime consistent with the dynamics shown by the synchronization of weakly coupled oscillators. On the other hand, deviations to high-CVE, appearing mostly during NREM sleep associated with EEG phasic activity and high-amplitude Gaussian waves, can be interpreted as the arrhythmic superposition of transient neural synchronization events. These two different manifestations of neural synchrony (low-CVE/high-CVE) explain the well-known spectral differences between REM and NREM sleep, while also illuminating the origin of the EEG 1/f spectrum.

Copper enhances cellular and network excitabilities, and improves temporal processing in the rat hippocampus.

Copper, an ion with many important metabolic functions, has also been proposed to have a role as modulator on neuronal function, mostly based on its effects on voltage- and neurotransmitter-gated conductance as well as on neurological symptoms of patients with altered copper homeostasis. Nevertheless, the mechanisms by which copper exerts its neuromodulatory effects have not been clearly established in a functional neuronal network. Using rat hippocampus slices as a neuronal network model, the effects of copper in the range of 10-100 nm were tested on the intrinsic, synaptic and network properties of the CA1 region. Most of the previously described effects of this cation were in the micromolar range of copper concentrations. The current results indicate that copper is a multifaceted neuromodulator, having effects that may be grouped into two categories: (i) activity enhancement, by modulating synaptic communication and action potential (AP) conductances; and (ii) temporal processing and correlation extraction, by improving reliability and depressing inhibition. Specifically it was found that copper hyperpolarizes AP firing threshold, enhances neuronal and network excitability, modifies CA3-CA1 pathway gain, enhances the frequency of spontaneous synaptic events, decreases inhibitory network activity, and improves AP timing reliability. Moreover, copper chelation by bathocuproine decreases spontaneous network spiking activity. These results allow the proposal that copper affects the network activity from cellular to circuit levels on a moment-by-moment basis, and should be considered a crucial functional component of hippocampal neuronal circuitry.

Extracellular recordings reveal absence of magneto sensitive units in the avian optic tectum.

There is a consensus that birds detect the earth's magnetic field and use some of its features for orientation and homing purposes. Since the late 1960s, when the first solid behavioral evidence of magnetoreception was obtained, much research has been devoted to describing the ethological aspects of this behavior. The neurophysiological basis of magnetoreception has been much less studied, although a frequently cited 1986 report described a high prevalence (70 %) of magneto-sensitive neurons in the pigeon optic tectum with high signal-to-noise ratios (Semm and Demaine, J Comp Physiol A 159:619-625, 1986). Here, we repeated these neurophysiological experiments using anesthetized as well as awake pigeons and new recording techniques. Our data indicate that magneto-sensitive units do not exist in the avian tectum.

Attentional capture? Synchronized feedback signals from the isthmi boost retinal signals to higher visual areas.

When a salient object in the visual field captures attention, the neural representation of that object is enhanced at the expense of competing stimuli. How neural activity evoked by a salient stimulus evolves to take precedence over the neural activity evoked by other stimuli is a matter of intensive investigation. Here, we describe in pigeons (Columba livia) how retinal inputs to the optic tectum (TeO, superior colliculus in mammals), triggered by moving stimuli, are selectively relayed on to the rotundus (Rt, caudal pulvinar) in the thalamus, and to its pallial target, the entopallium (E, extrastriate cortex). We show that two satellite nuclei of the TeO, the nucleus isthmi parvocelullaris (Ipc) and isthmi semilunaris (SLu), send synchronized feedback signals across tectal layers. Preventing the feedback from Ipc but not from SLu to a tectal location suppresses visual responses to moving stimuli from the corresponding region of visual space in all Rt subdivisions. In addition, the bursting feedback from the Ipc imprints a bursting rhythm on the visual signals, such that the visual responses of the Rt and the E acquire a bursting modulation significantly synchronized to the feedback from Ipc. As the Ipc feedback signals are selected by competitive interactions, the visual responses within the receptive fields in the Rt tend to synchronize with the tectal location receiving the "winning" feedback from Ipc. We propose that this selective transmission of afferent activity combined with the cross-regional synchronization of the areas involved represents a bottom-up mechanism by which salient stimuli capture attention.

From L'Homme Machine to metabolic closure: steps towards understanding life.

The nature of life has been a topic of interest from the earliest of times, and efforts to explain it in mechanistic terms date at least from the 18th century. However, the impressive development of molecular biology since the 1950s has tended to have the question put on one side while biologists explore mechanisms in greater and greater detail, with the result that studies of life as such have been confined to a rather small group of researchers who have ignored one another's work almost completely, often using quite different terminology to present very similar ideas. Central among these ideas is that of closure, which implies that all of the catalysts needed for an organism to stay alive must be produced by the organism itself, relying on nothing apart from food (and hence chemical energy) from outside. The theories that embody this idea to a greater or less degree are known by a variety of names, including (M,R) systems, autopoiesis, the chemoton, the hypercycle, symbiosis, autocatalytic sets, sysers and RAF sets. These are not all the same, but they are not completely different either, and in this review we examine their similarities and differences, with the aim of working towards the formulation of a unified theory of life.

Topographic arrangement of the rotundo-entopallial projection in the pigeon (Columba livia).

The tectofugal pathway (retina--optic tectum--nucleus rotundus--entopallium) is a prominent route mediating visual discrimination in diurnal birds. Several lines of evidence have shown that at the tecto-rotundal stage this pathway is composed of multiple parallel channels. Anatomical studies show that the nucleus rotundus is composed of at least four subdivisions, according to differences in cytoarchitectonic, histochemical, and hodological properties. Each of these subdivisions is in receipt of a highly convergent, nontopographic tectal projection, originating from a distinct subset of tecto-rotundal neurons. Physiological studies show that neurons of different subdivisions respond specifically to different visual dimensions, such as color, luminance, two-dimensional motion, and in-depth motion. At present it is less clear whether or to what extent this channel segregation is preserved at the telencephalic stage of the tectofugal pathway. The entopallium shows no obvious subdivisions or laminations. Nevertheless, tract-tracing experiments show that separate portions of the entopallium receive efferent projections from different rotundal subdivisions, in a way that maintains the rostrocaudal order of these subdivisions. In the present study we investigate in detail the topography of the rotundo-entopallial projection by means of anterograde and retrograde neuronal tracers. Our results confirm the zonal topography proposed by previous studies and indicate that each zone in the entopallium receives a direct and topographically organized projection from its corresponding rotundal subdivision. These results suggest that the spatial arrangement of the different rotundal functional modules is preserved at the entopallial level.

Closure to efficient causation, computability and artificial life.

The major insight in Robert Rosen's view of a living organism as an (M,R)-system was the realization that an organism must be "closed to efficient causation", which means that the catalysts needed for its operation must be generated internally. This aspect is not controversial, but there has been confusion and misunderstanding about the logic Rosen used to achieve this closure. In addition, his corollary that an organism is not a mechanism and cannot have simulable models has led to much argument, most of it mathematical in nature and difficult to appreciate. Here we examine some of the mathematical arguments and clarify the conditions for closure.

Amplitude modulation patterns of local field potentials reveal asynchronous neuronal populations.

Neural oscillations, which appear in several areas of the nervous system and cover a wide frequency range, are a prominent issue in current neuroscience. Extracellularly recorded oscillations are generally thought to be a manifestation of a neural population with synchronized electrical activity resulting from coupling mechanisms. The vertebrate olfactory neuroepithelium exhibits beta-band oscillations, termed peripheral waves (PWs), in their population response to odor stimulation. Here, we examine PWs in the channel catfish and propose that their properties could be explained as the superposition of asynchronous oscillators. Our model shows that the intriguing random pattern of amplitude-modulated PWs could be explained by Rayleigh fading, an interference phenomenon well known in physics and recognizable using statistical methods and signal analysis. We are proposing a mathematical fingerprint to characterize neural signals generated by the addition of random phase oscillators. Our interpretation of PWs as arising from asynchronous oscillators could be generalized to other neuronal populations, because it suggests that neural oscillations, detected in local field potential recordings within a narrow frequency band, do not necessarily originate from synchronization events.

A cholinergic gating mechanism controlled by competitive interactions in the optic tectum of the pigeon.

We describe the operation of a midbrain neural circuit in pigeons that may participate in selecting and attending to one visual stimulus from the myriad displayed in their visual environment. This mechanism is based on a topographically organized cholinergic signal reentering the optic tectum (TeO). We have shown previously that, whenever a visual stimulus activates neurons in a given tectal location, this location receives a strong bursting feedback from cholinergic neurons of the nucleus isthmi pars parvocellularis (Ipc), situated underneath the tectum. Here we show that, if a second visual stimulus is presented, even far from the first, the feedback signal to the first tectal location is diminished or suppressed, and feedback to the second tectal location is initiated. We found that this long-range suppressive interaction is mostly mediated by the nucleus isthmi pars magnocellularis, which sends a wide-field GABAergic projection to Ipc and TeO. In addition, two sets of findings indicate that the feedback from the Ipc modulates the ascending output from the TeO. First, visually evoked extracellular responses recorded in the dorsal anterior subdivision of the thalamic nucleus rotundus (RtDa), receiving the ascending tectal output, are closely synchronized to this feedback signal. Second, local inactivation of the Ipc prevents visual responses in RtDa to visual targets moving in the corresponding region of visual space. These results suggest that the ascending transmission of visual activity through the tectofugal pathway is gated by this cholinergic re-entrant signal, whose location within the tectal visual map is dynamically defined by competitive interactions.

Beyond reductionism: metabolic circularity as a guiding vision for a real biology of systems.

The definition of life has excited little interest among molecular biologists during the past half-century, and the enormous development in biology during that time has been largely based on an analytical approach in which all biological entities are studied in terms of their components, the process being extended to greater and greater detail without limit. The benefits of this reductionism are so obvious that they need no discussion, but there have been costs as well, and future advances, for example, for creating artificial life or for taking biotechnology beyond the level of tinkering, will need more serious attention to be given to the question of what makes a living organism living. According to Robert Rosen's theory of metabolism-replacement systems, the central idea missing from molecular biology is that of metabolic circularity, most evident from the obvious but commonly ignored fact that proteins are not given from outside but are products of metabolism, and thus metabolites. Among other consequences, this implies that the usual distinction between proteome and metabolome is conceptually artificial -- however useful it may be in practice -- as the proteome is part of the metabolome.

Organizational invariance and metabolic closure: analysis in terms of (M,R) systems.

This article analyses the work of Robert Rosen on an interpretation of metabolic networks that he called (M,R) systems. His main contribution was an attempt to prove that metabolic closure (or metabolic circularity) could be explained in purely formal terms, but his work remains very obscure and we try to clarify his line of thought. In particular, we clarify the algebraic formulation of (M,R) systems in terms of mappings and sets of mappings, which is grounded in the metaphor of metabolism as a mathematical mapping. We define Rosen's central result as the mathematical expression in which metabolism appears as a mapping f that is the solution to a fixed-point functional equation. Crucially, our analysis reveals the nature of the mapping, and shows that to have a solution the set of admissible functions representing a metabolism must be drastically smaller than Rosen's own analysis suggested that it needed to be. For the first time, we provide a mathematical example of an (M,R) system with organizational invariance, and we analyse a minimal (three-step) autocatalytic set in the context of (M,R) systems. In addition, by extending Rosen's construction, we show how one might generate self-referential objects f with the remarkable property f(f)=f, where f acts in turn as function, argument and result. We conclude that Rosen's insight, although not yet in an easily workable form, represents a valuable tool for understanding metabolic networks.

Oscillatory bursts in the optic tectum of birds represent re-entrant signals from the nucleus isthmi pars parvocellularis.

Fast oscillatory bursts (OBs; 500-600 Hz) are the most prominent response to visual stimulation in the optic tectum of birds. To investigate the neural mechanisms generating tectal OBs, we compared local recordings of OBs with simultaneous intracellular and extracellular single-unit recordings in the tectum of anesthetized pigeons. We found a specific population of units that responded with burst discharges that mirrored the burst pattern of OBs. Intracellular filling with biocytin of some of these bursting units demonstrated that they corresponded to the paintbrush axon terminals from the nucleus isthmi pars parvocellularis (Ipc). Direct recordings in the Ipc confirmed the high correlation between Ipc cell firing and tectal OBs. After injecting micro-drops of lidocaine in the Ipc, the OBs of the corresponding tectal locus disappeared completely. These results identify the paintbrush terminals as the neural elements generating tectal OBs. These terminals are presumably cholinergic and ramify across tectal layers in a columnar manner. Because the optic tectum and the Ipc are reciprocally connected such that each Ipc neuron sends a paintbrush axon to the part of the optic tectum from which its visual inputs come, tectal OBs represent re-entrant signals from the Ipc, and the spatial-temporal pattern of OBs across the tectum is the mirror representation of the spatial-temporal pattern of bursting neurons in the Ipc. We propose that an active location in the Ipc may act, via bursting paintbrushes in the tectum, as a focal "beam of attention" across tectal layers, enhancing the saliency of stimuli in the corresponding location in visual space.

Understanding the parts in terms of the whole.

Metabolism is usually treated as a set of chemical reactions catalysed by separate enzymes. However, various complications, such as transport of molecules across membranes, physical association of different enzymes, giving the possibility of metabolite channelling, need to be taken into account. More generally, a proper understanding of the nature of life will require metabolism to be treated as a complete system, and not just as a collection of components. Certain properties of metabolic systems, such as feedback inhibition of the first committed step of a pathway, make sense only if one takes a broader view of a pathway than is usual in textbooks, so that one can appreciate ideas such as regulation of biosynthesis according to demand. More generally still, consideration of metabolism as a whole puts the emphasis on certain systemic aspects that are crucial but which can pass unnoticed if attention is always focussed on details. For example, a living organism, unlike any machine known or conceivable at present, makes and maintains itself and all of its components. Any serious investigation of how this can be possible implies an infinite regress in which each set of enzymes needed for the metabolic activity of the organism implies the existence of another set of enzymes to maintain them, which, in turn, implies another set, and so on indefinitely. Avoiding this implication of infinite regress represents a major challenge for future investigation.

The mapping of the visual field onto the dorso-lateral tectum of the pigeon (Columba livia) and its relations with retinal specializations.

Most of the physiological studies of the pigeon retino-tectal visual pathway have investigated the accessible tectum, a small dorso-lateral tectal section that can be easily accessed by a simple craniotomy. However, at present we lack a detailed study of the topographical arrangement between the visual field, the retina and the accessible tectum. In particular, it is not known which section of the visual field is mapped onto the accessible tectum, and which of the specialized retinal areas mediates this projection. Here we determined, using local field potential (LFP) recordings and reverse retinoscopy, the shape, size and position in the visual space of the portion of the visual field mapped onto the accessible tectum (called here the accessible visual field, or AVF). Using this data and the mapping of Nalbach et al. [Vis. Res. 30 (4) (1990) 529], the retinal area corresponding to the AVF was determined. Such retinal area was also directly delimited by means of retrograde transport of DiI. The results indicate that the AVF is a triangular perifoveal zone encompassing only 15% of total visual field. The retinal region corresponding to the AVF has the shape of an elongated triangle that runs parallel to the visual equator and contains the fovea, the tip of the pecten, a perifoveal region of the yellow field and a small crescent of the red field. In agreement with this anatomical heterogeneity, visual evoked potentials measured in different parts of the accessible tectum present steep variations in shape and size. These results are helpful to better design and interpret anatomical and physiological experiments involving the pigeon's visual system.

Autopoietic and (M,R) systems.

From the many attempts to produce a conceptual framework for the organization of living systems, the notions of (M,R) systems and Autopoiesis stand out for their rigor, their presupposition of the circularity of metabolism, and the new epistemologies that they imply. From their inceptions, these two notions have been essentially disconnected because each has defined its own language and tools. Here we demonstrate the existence of a deep conceptual link between (M,R) systems and Autopoietic systems. This relationship permits us to posit that Autopoietic systems, which have been advanced as capturing the central aspects of living systems, are a subset of (M,R) systems. This result, in conjunction with previous theorems proved by Rosen, can be used to outline a demonstration that the operation of Autopoietic systems cannot be simulated by Turing machines. This powerful result shows the potential of linking these two models. Finally, we suggest that the formalism of (M,R) systems could be used to model the circularity of metabolism.

Spatial organization of the pigeon tectorotundal pathway: an interdigitating topographic arrangement.

The retinotectofugal system is the main visual pathway projecting upon the telencephalon in birds and many other nonmammalian vertebrates. The ascending tectal projection arises exclusively from cells located in layer 13 of the optic tectum and is directed bilaterally toward the thalamic nucleus rotundus. Although previous studies provided evidence that different types of tectal layer 13 cells project to different subdivisions in Rt, apparently without maintaining a retinotopic organization, the detailed spatial organization of this projection remains obscure. We reexamined the pigeon tectorotundal projection using conventional tracing techniques plus a new method devised to perform small deep-brain microinjections of crystalline tracers. We found that discrete injections involving restricted zones within one subdivision retrogradely label a small fraction of layer 13 cells that are distributed throughout the layer, covering most of the tectal representation of the contralateral visual field. Double-tracer injections in one subdivision label distinct but intermingled sets of layer 13 neurons. These results, together with the tracing of tectal axonal terminal fields in the rotundus, lead us to propose a novel "interdigitating" topographic arrangement for the tectorotundal projection, in which intermingled sets of layer 13 cells, presumably of the same particular class and distributed in an organized fashion throughout the surface of the tectum, terminate in separate regions within one subdivision. This spatial organization has significant consequences for the understanding of the physiological and functional properties of the tectofugal pathway in birds.