Volume 20, Number 4
December 2013
Developing Neural Networks and Plasticity
T
here is mounting evidence that the role of astrocytes in central nervous system development, networking, and plasticity is more than significant. Once regarded as mostly supportive and protective of neuronal function—the neuron traditionally considered the more evolved brain cell—recent neuroscientific advances from functional magnetic resonance imaging (fMRI) and other interface technologies force us to reconsider the hierarchy of brain control. Pereira and Furlan1 propose an astrocentric theory for the role of astrocytes in cognition and behavior. In this theory, the neuronal pool functions to provide an unconscious “awareness” of our state via tripartite synapses to “Local hubs” subserved by protoplasmic astrocytes, while the widespread astrocytic syncytium (composed of all 5 astrocyte types) or “Master hub” correlates pooled data from neurons, the blood-brain barrier, cerebrospinal fluid, and other internal milieu (“panglial syncytium”) to make a final “judgment” that at some point crosses the threshold to human consciousness and behavior. The authors relate the Master hub function of astrocytes with the default mode network first described in fMRI, an imaging modality wholly dependent on measuring the blood oxygen level (or BOLD signal) in cortical capillaries. Notably, the part of the human default mode network that is active only in conscious states is identified as a slow cortical potential by He and Raichle.2 In this Seminar, the first article serves to remind us of the important early role the astrocytes play in central nervous system development and, notably, their continued development in postnatal life, and their known function in synaptic plasticity. We find there is a relative paucity of information to date regarding astrocyte function when compared with what we know about neuronal function. The second article attests to the fact that a growing number of heretofore poorly understood neurologic disorders are now becoming associated with a primary disorder in astrocytic function. As mentioned, advances in fMRI research have established an observable “default mode network” that correlates with our resting (or restorative) state and is measurable as a physiologic ultradian or very low-frequency rhythm (the slow cortical potential). The third article reviews the evidence that recordable very low-frequency brain rhythms are nonneuronal in origin and are coupled to the cyclic adenosine triphosphate derived from astrocyte metabolism. We are now 1071-9091/13/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2013.10.002
intrigued by the realization that the brain's resting state networks are driven not by neurons but by a constellation of astrocytes constantly modifying interneuronal communications, and that mechanisms of neuroplasticity allowing for restoration of function must lie within this scheme. The fourth article describes clinical approaches to access these resting state or default mode circuits. Neuromodulation of resting networks enhances mechanisms for plasticity and promotes restoration of function. Exogenous modes of neuromodulation are represented by magnetic brain stimulation, deep brain stimulation, and vagus nerve stimulation among others. It emphasizes the relevance of an endogenous strategy, of importance especially in pediatric and adolescent populations (the immature brain) to reroute maladaptive developmental trajectories. It posits a hierarchy of control within brain networks and suggests the need to achieve first a downregulation of neuronal excitability to facilitate the renormalization of maladapted resting state network connectivity. Improvement in sleep architecture, autonomic balance, and homeodynamic regulation set the stage for addressing central nervous system instabilities such as seizures, migraines, asthma, and panic, as well as issues of state regulation generally (eg, attention-deficit hyperactivity disorder). The fifth and last article is a physician's brief perspective in utilizing this noninvasive endogenous neuromodulatory technique as part of routine medical practice and the medical diagnoses most likely to derive benefit from this form of neurotherapy. Sit back and enjoy this Seminar's brief exploration into inner space: the glia galactica. Stella B. Legarda, MD Peninsula Primary Care Specialty Clinics, Carmel, CA Associate Professor, Neurology and Pediatrics University of Vermont Guest Editor
References 1. Pereira, Furlan: Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity. Prog Neurobiol 92:405-420, 2010 2. He BJ, Raichle ME: The fMRI signal, slow cortical potential and consciousness. Trends Cogn Sci 13:302-309, 2009, (2009)
229
December 2013
Developing Neural Networks and Plasticity
T
here is mounting evidence that the role of astrocytes in central nervous system development, networking, and plasticity is more than significant. Once regarded as mostly supportive and protective of neuronal function—the neuron traditionally considered the more evolved brain cell—recent neuroscientific advances from functional magnetic resonance imaging (fMRI) and other interface technologies force us to reconsider the hierarchy of brain control. Pereira and Furlan1 propose an astrocentric theory for the role of astrocytes in cognition and behavior. In this theory, the neuronal pool functions to provide an unconscious “awareness” of our state via tripartite synapses to “Local hubs” subserved by protoplasmic astrocytes, while the widespread astrocytic syncytium (composed of all 5 astrocyte types) or “Master hub” correlates pooled data from neurons, the blood-brain barrier, cerebrospinal fluid, and other internal milieu (“panglial syncytium”) to make a final “judgment” that at some point crosses the threshold to human consciousness and behavior. The authors relate the Master hub function of astrocytes with the default mode network first described in fMRI, an imaging modality wholly dependent on measuring the blood oxygen level (or BOLD signal) in cortical capillaries. Notably, the part of the human default mode network that is active only in conscious states is identified as a slow cortical potential by He and Raichle.2 In this Seminar, the first article serves to remind us of the important early role the astrocytes play in central nervous system development and, notably, their continued development in postnatal life, and their known function in synaptic plasticity. We find there is a relative paucity of information to date regarding astrocyte function when compared with what we know about neuronal function. The second article attests to the fact that a growing number of heretofore poorly understood neurologic disorders are now becoming associated with a primary disorder in astrocytic function. As mentioned, advances in fMRI research have established an observable “default mode network” that correlates with our resting (or restorative) state and is measurable as a physiologic ultradian or very low-frequency rhythm (the slow cortical potential). The third article reviews the evidence that recordable very low-frequency brain rhythms are nonneuronal in origin and are coupled to the cyclic adenosine triphosphate derived from astrocyte metabolism. We are now 1071-9091/13/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2013.10.002
intrigued by the realization that the brain's resting state networks are driven not by neurons but by a constellation of astrocytes constantly modifying interneuronal communications, and that mechanisms of neuroplasticity allowing for restoration of function must lie within this scheme. The fourth article describes clinical approaches to access these resting state or default mode circuits. Neuromodulation of resting networks enhances mechanisms for plasticity and promotes restoration of function. Exogenous modes of neuromodulation are represented by magnetic brain stimulation, deep brain stimulation, and vagus nerve stimulation among others. It emphasizes the relevance of an endogenous strategy, of importance especially in pediatric and adolescent populations (the immature brain) to reroute maladaptive developmental trajectories. It posits a hierarchy of control within brain networks and suggests the need to achieve first a downregulation of neuronal excitability to facilitate the renormalization of maladapted resting state network connectivity. Improvement in sleep architecture, autonomic balance, and homeodynamic regulation set the stage for addressing central nervous system instabilities such as seizures, migraines, asthma, and panic, as well as issues of state regulation generally (eg, attention-deficit hyperactivity disorder). The fifth and last article is a physician's brief perspective in utilizing this noninvasive endogenous neuromodulatory technique as part of routine medical practice and the medical diagnoses most likely to derive benefit from this form of neurotherapy. Sit back and enjoy this Seminar's brief exploration into inner space: the glia galactica. Stella B. Legarda, MD Peninsula Primary Care Specialty Clinics, Carmel, CA Associate Professor, Neurology and Pediatrics University of Vermont Guest Editor
References 1. Pereira, Furlan: Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity. Prog Neurobiol 92:405-420, 2010 2. He BJ, Raichle ME: The fMRI signal, slow cortical potential and consciousness. Trends Cogn Sci 13:302-309, 2009, (2009)
229
