In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic (...) mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

This article argues that mirror neurons originate in sensorimotor associative learning and therefore a new approach is needed to investigate their functions. Mirror neurons were discovered about 20 years ago in the monkey brain, and there is now evidence that they are also present in the human brain. The intriguing feature of many mirror neurons is that they fire not only when the animal is performing an action, such as grasping an object using a power grip, but also when the (...) animal passively observes a similar action performed by another agent. It is widely believed that mirror neurons are a genetic adaptation for action understanding; that they were designed by evolution to fulfill a specific socio-cognitive function. In contrast, we argue that mirror neurons are forged by domain-general processes of associative learning in the course of individual development, and, although they may have psychological functions, they do not necessarily have a specific evolutionary purpose or adaptive function. The evidence supporting this view shows that mirror neurons do not consistently encode action “goals”; the contingency- and context-sensitive nature of associative learning explains the full range of mirror neuron properties; human infants receive enough sensorimotor experience to support associative learning of mirror neurons ; and mirror neurons can be changed in radical ways by sensorimotor training. The associative account implies that reliable information about the function of mirror neurons can be obtained only by research based on developmental history, system-level theory, and careful experimentation. (shrink)

Musical improvisation is a sophisticated activity in which a performer realizes, real-time, melodic, and rhythmic sequences in harmony with those from other musicians. The study of musical improvisation helps one to understand not only the cognition of creativity, but also the complex neuronal basis of executive functions, the relation between conscious and unconscious action, and even more. So far, the prevailing models, founded on the brain imaging method, have focused on the connection between the cortical areas and their cognitive (...) processes. Little attention, on the other hand, has been given to the huge variety of subcortical activities, especially in the basal ganglia. This fundamental subcortical component, through its implicit procedures and the role it plays in memory, is responsible to produce new information all the time, allowing the prefrontal cortex to transform a huge and disordered amount of data in explicit creative acts. The basal ganglia are strongly related to the activation of chemical signals generated by dissonance or lack of symmetry between perception and expectation, participating even in the responses to environmental demands according to the circumstances. Thus, they interact with the frontal cortex and with the limbic system, playing a key role in planning and selecting appropriate actions and in decision making. In this text, we try to explain in which sense improvisation is connected to the processes of executive functions, to creativity and to the integrated activity of cortical–subcortical areas controlling the free flow of ideas and to expressive spontaneity. Eventually, we purpose a model according to which structure and process take part at the centrencephalic space of functional integration, which, through both competing and cooperating dynamics, gives way to spontaneous composition. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Millikan’s (1984. Language, Thought, and Other Biological Categories: New Foundations for Realism. MIT Press) selected effects theory of functions states that functions are effects for which the ancestors of a trait were selected for. As the function is an effect a thing’s ancestors produced, only things that are reproductions in some sense can have functions. Against this reproduction requirement, Garson (2019. What Biological Functions Are and Why They Matter. Cambridge University Press) argues that not only processes of differential reproduction (...) but also processes of differential persistence can lead to new functions. Since such “persistence functions” have the same explanatory power as traditional selected effects functions, selected effects theorists should include them in their theory. In this paper, I will defend Millikan’s theory against this argument. I will show that the proponents of the generalized theory have yet to provide a working notion of populations that avoids a liberality problem. Further, I will argue that persistence functions are at best a marginal case of functions due to their restricted explanatory power. (shrink)

Myelin is required for efficient nerve conduction, but not all axons are myelinated to the same extent. Here we review recent studies that have revealed distinct myelination patterns of different axonal paths, suggesting that myelination is not an all or none phenomenon and that its presence is finely regulated in central nervous system networks. Whereas powerful reductionist biology has led to important knowledge of how oligodendrocytes function by themselves, little is known about their role in neuronal networks. We (...) still do not understand how oligodendrocytes integrate information from neurons to adapt their function to the need of the system. An intricate cross talk between neurons and glia is likely to exist and to determine how neuronal circuits operate as a whole. Dissecting these mechanisms by using integrative systems biology approaches is one of the major challenges ahead. (shrink)

The functional role of mirror neurons has been assessed in many different ways. They have been regarded, inter alia, as the core mechanism of mind reading, the mechanism of language understanding, the mechanism of imitation. In this paper we will discuss the thesis according to which MNs are a conceptual mechanism. This hypothesis is attractive since it could accommodate in an apparently simple way all the above-mentioned interpretations. We shall take into consideration some reasons suggesting the conceptualist characterization of MNs, (...) as well as some possible replies. We shall figure out how an argument for the conceptualist hypothesis could be deployed, focusing on the notion of off-line processes, which turns out to be the crucial property necessary to ascribe concept possession. Our conclusion will be that, despite of there being some evidence for the conceptualist account, the issue cannot be definitely settled, because there are both experimental shortages and conceptual difficulties. In particular, there are three distinct senses in which MNs can be regarded as a conceptual mechanism, but we shall argue that only one of these interpretations can be defended. (shrink)

The transplantation of cholinergic neurons into the hippocampal formation has been well characterized. We describe our studies on the effects of cholinergic transplants in the retrosplenial cortex. These transplants were capable of ameliorating spatial navigation deficits in rats with septohippocampal lesions. In addition, we provide evidence for the modulation of transplanted neurons by the host brain.

A new class of visuomotor neuron has been recently discovered in the monkey’s premotor cortex: mirror neurons. These neurons respond both when a particular action is performed by the recorded monkey and when the same action, performed by another individual, is observed. Mirror neurons appear to form a cortical system matching observation and execution of goal-related motor actions. Experimental evidence suggests that a similar matching system also exists in humans. What might be the functional role of this matching system? One (...) possible function is to enable an organism to detect certain mental states of observed conspecifics. This function might be part of, or a precursor to, a more general mind-reading ability. Two different accounts of mind-reading have been suggested. According to “theory theory‘, mental states are represented as inferred posits of a naive theory. According to “simulation theory‘, other people’s mental states are represented by adopting their perspective: by tracking or matching their states with resonant states of one’s own. The activity of mirror neurons, and the fact that observers undergo motor facilitation in the same muscular groups as those utilized by target agents, are findings that accord well with simulation theory but would not be predicted by theory theory. (shrink)

In this chapter, I aim to examine the two central properties that are said to underlie the theory of mirror neurons, namely action execution and action observation. I shall call these the functional properties of mirror neurons. I will argue that attributing the functional properties of mirror cognition, as many neuroscientists do, to the so-called ‘mirror neurons’ suffers from the problem of misidentification. This is the problem of incorrectly identifying an object or a property of one sort with some other (...) object or property. In light of this, I will propose that the most promising solution for the problem of misidentification is to ground the functional properties of mirror neurons squarely in consciousness and its bearer. (shrink)

Recently, there has been a resurgence of interest in theories of mindreading. New discoveries in neuroscience have revitalized the languishing debate. The discovery of so-called mirror neurons has revived interest particularly in the Simulation Theory (ST) of mindreading. Both ST proponents and theorists studying mirror neurons have argued that mirror neurons are strong evidence in favor of ST over Theory Theory (TT). In this paper I argue against the prevailing view that mirror neurons are evidence for the ST of mindreading. (...) My view is that on an appropriate construal of their function, mirror neurons do not operate like simulation theorists claim. In fact, mirror neurons are more appropriately understood as one element in an information-rich mindreading process. As such, mirror neurons fit in better with some sort of TT account of mindreading. I offer a positive account, the Model TT, which better explains the role of mirror neurons in social cognition. (shrink)

The main idea -- The functioning of a neuron -- Brain structure and function -- The general structure of the neural network -- Instincts, emotions, free will -- The nature of mental objects -- The rise and essence of (self-)consciousness -- Artificial intelligence -- Cognitive limitations of man.

In numerous peripheral sense organs, external stimuli are detected by primary sensory neurons compartmentalized within specialized structures composed of cuticular or epithelial tissue. Beyond reflecting developmental constraints, such compartmentalization also provides opportunities for grouped neurons to functionally interact. Here, the authors review and illustrate the prevalence of these structural units, describe characteristics of compartmentalized neurons, and consider possible interactions between these cells. This article discusses instances of neuronal crosstalk, examples of which are observed in the vertebrate tastebuds and multiple (...) types of arthropod chemosensory hairs. Particular attention is paid to insect olfaction, which presents especially well‐characterized mechanisms of functional, cross‐neuronal interactions. These examples highlight the potential impact of peripheral processing, which likely contributes more to signal integration than previously considered. In surveying a wide variety of structural units, it is hoped that this article will stimulate future research that determines whether grouped neurons in other sensory systems can also communicate to impact information processing. (shrink)

Traditionally, the impairment of cognitive functions in Alzheimeŕs disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large‐scale networks, with a variety of electrophysiological and imaging techniques have revealed (...) two forms of AD‐related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches. (shrink)

The neurological discovery of mirror neurons is of eminent importance for the phenomenological theory of intersubjectivity. G. Rizzolatti and V. Gallese found in experiments with primates that a set of neurons in the premotor cortex represents the visually registered movements of another animal. The activity of these mirror neurons presents exactly the same pattern of activity as appears in the movement of one's own body. These findings may be extended to other cognitive and emotive functions in humans. I show how (...) these neurological findings might be “translated” phenomenologically into our own experienced sensations, feelings and volitions. (shrink)

In contrast to the views put forth by Stein & Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.

Recent research suggests that human memories are stored not between neurons as synaptic weights, but within individual neurons themselves. This opens the possibility to replace the dominant paradigm of brain function – neural networks – with a new one. In this article, I explore how “identified neurons” could explain how memories are stored, and how human traits are implemented in the brain.

Neurons of organisms with complex and flexible behavior, especially humans, must precisely control protein localization and activity to support higher brain functions such as learning and memory. In contrast, simpler organisms generally have simpler individual neurons, less complex nervous systems and display more limited behaviors. Strikingly, however, many key neuronal proteins are conserved between organisms that have very different degrees of behavioral complexity. Here we discuss a possible mechanism by which conserved neuronal proteins acquired new attributes that were (...) crucial in the evolution of complexity of nervous system structure and function. Specifically, we hypothesize that vertebrate‐specific post‐translational palmitoylation sites and PDZ‐binding protein‐protein interaction motifs act as gain‐of‐function mutations, increasing the regulatory potential of conserved proteins without affecting their core functions. We further hypothesize that the additional regulation of neurotransmitter receptors and other membrane proteins made possible by these sites and motifs is critical for the function of complex nervous systems. (shrink)

Foetal neurones transplanted within the adult mammalian central nervous system survive and differentiate. Study of such transplants has yielded insights into the function, development and plasticity of brain structures, and suggests promising new therapies for a number of neurological disorders.

A formalism is introduced to represent the connective organization of an evolving neuronal network and the effects of environment on this organization by stabilization or degeneration of labile synapses associated with functioning. Learning, or the acquisition of an associative property, is related to a characteristic variability of the connective organization: the interaction of the environment with the genetic program is printed as a particular pattern of such organization through neuronal functioning. An application of the theory to the development (...) of the neuromuscular junction is proposed and the basic selective aspect of learning emphasized. (shrink)

How does neuronal activity give rise to cognitive capacities? To address this question, neuroscientists hypothesize about what neurons “represent,” “encode,” or “compute,” and test these hypotheses empirically. This process is similar to the assessment of hypotheses in other fields of science and as such is subject to the same limitations and difficulties that have been discussed at length by philosophers of science. In this paper, we highlight an additional difficulty in the process of empirical assessment of hypotheses that is (...) unique to the cognitive sciences. We argue that, unlike in other scientific fields, comparing hypotheses according to the extent to which they explain or predict empirical data can lead to absurd results. Other considerations, which are perhaps more subjective, must be taken into account. We focus on one such consideration, which is the purposeful function of the neurons as part of a biological system. We believe that progress in neuroscience critically depends on properly addressing this difficulty. (shrink)

Different theories have been proposed for explaining the evolution of language. One of this maintains that gestural communication has been the precursor of human speech. Here we present a series of neurophysiological evidences that support this hypothesis. Communication by gestures, defined as the capacity to emit and recognize meaningful actions, may have originated in the monkey motor cortex from a neural system whose basic function was action understanding. This system is made by neurons of monkey’s area F5, named mirror (...) neurons, activated by both execution and observation of goal-related actions. Recently, two new categories of mirror neurons have been described. Neurons of one category respond to the sound of an action, neurons of the other category respond to the observation of mouth ingestive and communicative actions. The properties of these neurons indicate that monkey’s area F5 possesses the basic neural mechanisms for associating gestures and meaningful sounds as a pre-adaptation for the later emergence of articulated speech. The homology and the functional similarities between monkey area F5 and Broca’s area support this evolutionary scenario. (shrink)

Sentences such as "The author started the book" are indeterminate because they do not make explicit what the subject (the author) started doing with the object (the book). In principle, indeterminate sentences allow for an infinite number of interpretations. One theory, however, assumes that these sentences are resolved by semantic coercion, a linguistic process that forces the noun "book" to be interpreted as an activity (e.g., writing the book) or by a process that interpolates this activity information in the resulting (...) enriched semantic composition. An alternative theory, pragmatic, assumes classical semantic composition, whereby meaning arises from the denotation of words and how they are combined syntactically, with enrichment obtained via pragmatic inferences beyond linguistic-semantic processes. Cognitive neuroscience studies investigating the neuroanatomical and functional correlates of indeterminate sentences have shown activations either at the ventromedial pre-frontal cortex or at the left inferior frontal gyrus. These studies have supported the semantic coercion theory assuming that one of these regions is where enriched semantic composition takes place. Employing fMRI, we found that indeterminate sentences activate bilaterally the superior temporal gyrus, the right inferior frontal gyrus, and the anterior cingulate cortex, more so than control sentences ("The author wrote the book"). Activation of indeterminate sentences exceeded that of anomalous sentences ("…drank the book") and engaged more left- and right-hemisphere areas than other sentence types. We suggest that the widespread activations for indeterminate sentences represent the deployment of pragmatic-inferential processes, which seek to enrich sentence content without necessarily resorting to semantic coercion. (shrink)

The shapes of neurons and glial cells dictate many important aspects of their functions. In olfactory systems, certain architectural features are characteristics of these two cell types across a wide variety of species. The accumulated evidence suggests that these common features may play fundamental roles in olfactoryinformation processing. For instance, the primary olfactory neuropil in most vertebrate and invertebrate olfactory systems is organized into discrete modules called glomeruli. Inside each glomerulus, sensory axons and CNS neurons branch and synapse in patterns (...) that are repeated across species. In many species, moreover, the glomeruli are enveloped by a thin and ordered layer of glial processes. Theglomerular arrangement reflects the processing of odor information in modules that encode the discrete molecular attributes of odorant stimuli being processed. Recent studies of the mechanisms that guide the development of olfactory neurons and glial cells have revealed complex reciprocal interactions between these two cell types, which may be necessary for the establishment of modular compartments. Collectively, the findings reviewed here suggest that specialized cellular architecture plays key functional roles in the detection, analysis, and discrimination of odors at early steps in olfactory processing. (shrink)