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NanoneuroscienceNanoneuroscience Nancy Woolf, Avner Priel & Jack Tuszynski, UCLA and University of Alberta Springer INTRODUCTION: This book examines the connections between the cytoskeleton and the neural membrane and synapses, and the possible role of the cytoskeleton in neural processing, and learning and memory. The main import of the book is to argue that the cytoskeleton has a central role in neural processes that is more orthodoxly ascribed just to the cell membrane and synapses. The controversial question as to a possible role for the cytoskeleton in consciousness is only discussed in a rather muddled final chapter. In this respect the book is disappointing in failing to engage with the implications of the discovery of functional quantum coherence in photosynthetic organisms. The role of tryptophan in the cytoskeleton is mentioned, but not the significance of its resemblance to the coherent structures seen in photosynthetic light-harvesting. The cytoskeleton and the scaffolding proteins are here viewed as a computational network linked to the cell membrane and synapses. Neurons have three types of cytoskeletal protein, neurofilaments, microfilaments and microtubules. Neurofilaments only occur in neurons. These have a central α-helical rod, plus N and C termini that bind the molecules of the filament head-to-tail. The neurofilaments can form cross bridges with other cytoskeletal proteins. Neurofilaments are especially concentrated in axons. Control of the movement of synaptic proteins by the cytoskeleton is suggestive of a role in actually regulating the synapses. The activity of microtubules in neurons is markedly different from other cells. Microtubules are here more important for linking parts of the cell, such as taking synaptic vesicles from the Golgi apparatus in the cell body down to the axon terminal, and carrying protein and RNA to the dendritic spines. The book argues for interactivity between dendritic spines and the dendritic cytoskeleton. The dendritic spines can be modulated by actin indicating that cytoskeletal proteins can influence synaptic plasticity. The spines receive glutamate inputs by means of NMDA and AMPA receptors. Actin holds signal transduction molecules close to the NMDA receptors, and this links these receptors to signal cascades within the neuron. Actin is also important for anchoring ion channels, and congregating them in clusters. Actin filaments are known to control the excitability of some ion channels, such as the K+ channel, and it also binds to the Na+ and Ca2+ ion channels. Scaffolding proteins such as the post synaptic density protein, PSD95 and gephyrin a GABA receptor scaffolding protein, secure the membrane receptors in the dendritic spine, and attach them to protein kinases and also to actin filaments that constitute part of the cytoskeleton. Gephyrin concentrates GABA receptors at post synaptic sites, while actin filaments support the movements of geyphrin complexes. Actin filaments are concentrated immediately below the neuronal membrane, but also penetrate into the rest of the cytoskeleton and are heavily concentrated in dendritic spines. The actin filaments are shown to be involved in the reorganisation of dendritic spines following stimulation. They also hold in place receptors, ion channels and transduction molecules. Cell adhesion molecules such as neurologin and neurexin link the presynaptic to the postsynaptic membrane and keep neurons and also glia cell close enough for the transmission of neurotransmitters, neuromodulators etc. Neurologin binds to PSD95 protein in the postsynaptic membrane, and connects NMDA receptors and signal cascades, while neurexin binds to presynaptic membranes. Cell adhesion molecules also bind to one another. Cadherin molecules link actin in the pre and postsynaptic areas via another protein α-catenin. The cytoskeleton is suited to the propagation of signals. A number of studies indicate that actin filaments can act as a form of electric cable. The filaments of the cytoskeleton have condensations of counterions on their surface, and may also have charged groups that interact with counterions. Positive ions surround the negative charge of the filament protein. The filaments are often grouped close together, the presence of counterions overcoming repulsive forces in the protein molecules. Experimental studies have shown that ions are able to flow along the filament, thus conducting electric charge, without much impact on the environment around the filaments. The actin filaments also respond to the electrical fields around them. The electrical properties of tubulin determine the assembly of microtubules, their binding with other proteins and their transmission of signals. Tubulin has a Beta-sheet core surrounded by α-helices. The N terminus is close to the interface between these, and is the site for binding GTP or GDP. The value of the tubulin’s dipole moment is determined by which of these is bound. The crystallised structure of tubulin is now well understood except for the C-termini region. Unfortunately, it is this region that is important for the binding of microtubules and microtubule associated proteins (MAPs). The stability and ability to transmit signals of microtubules relates to their binding to MAPs. Tubulins are electronegative with positive pockets, but the C-termini are almost completely negative, and may contain half the electronegative charge of the whole tubulin. The tubulin comes in alternating alpha and beta tubulin monomers. The bonds between tubulins determine some of the properties of the microtubule. The alpha tubulin tends to a straight conformation and the beta tubulin to a curved conformation. This is thought to relate to the fact that GTP hydrolyses to GDP at the beta tubulin, but remains intact at the alpha tubulin. Microtubules are viewed as remarkable for their strength and resilience. The exterior of the microtubules is predominantly electronegative. Positive charge is concentrated in the areas between the 13 protofilaments that make up a microtubule. Microtubules are described as ferroelectric because they have spontaneous dipole moments. Dipole-to-dipole interactions can travel down the microtubule as a form of soliton. A double well within the tubulin dimer can be localised either to the alpha or the beta tubulin. Experimental studies indicate that microtubules amplify signals passed along them. This is related to the positive ion cloud attracted by the negative charged exterior of the microtubule. This view is also supported by theoretical modelling. It is thought probable that the C-termini of the tubulins react with ionic waves along the outside of the microtubules, and there are likely to be multiple conformations of the C-termini. These can interact with the tubulin, with one another and with MAPs. Ionic waves could become coupled to changes in C-termini. The states of the tubulin itself could be coupled to the C-termini and the surrounding ion clouds. The idea of signalling along microtubules contrasts with the orthodoxy that all neural signalling is along the cell membrane. The connection between the membrane and the cytoskeleton has tended to be ignored. Actin filaments are concentrated in dendritic spines and near to axon terminals. These bind to scaffolding proteins and interact with signalling molecules. There are also interactions between ion channels and the cytoskeleton, especially actin filaments. Experimental work suggests that the cytoskeleton and actin filaments in particular can regulate ion channels that are part of basic neural processing. Recent studies indicate cross linker proteins between actin filaments and microtubules, in additions to MAP 2 and tau which are known to bind to actin filaments. Dipole-to-dipole interaction in microtubules is due to the coupling of tubulin to six neighbouring tubulins, and this may lead to a signal propagating down the microtubule. The interior of the tubulin protein has two areas of positive charge separated by a negative region, so as to create a double well potential, which an electron could tunnel between. The long chains of tubulin appear able to facilitate coherent activity. Tubulin dimers could compute along with their neighbours and this could propagate along the chain. The architecture of thirteen strands in a lattice could be suitable for computing. The interior of the neuron is suggested to be well arranged for self-organisation, and has the potential to expand the computing power of the more orthodox membrane/synapse based model. Tubulin has two conformations, one binding to tau and the other to kinesin. Tau and MAP2 may between them regulate the conformation of tubulin and shifts in tubulin may in turn influence tau, MAP2 and kinesin allowing autonomous development within the neuron. Studies indicate changes in the cytoskeleton in response to learning and memory. The post-synaptic membrane can be altered in learning and this change can extend down to the cytoskeletal level. A more controversial suggestion is that it is the cytoskeleton that encodes long-term information. Studies support the idea of microtubules being reorganised in line with learning and memory. MAP2 found only in dendrites is suggested to be particularly important for memory. The most often discussed change in the brain in relation to learning and memory is long term potentiation (LTP), in which enhanced output of synapses following a stimulus is demonstrated. However LTP decays within at most 25 days, whereas a memory can last for a lifetime. Storage of information by biomolecules within neurons is suggested as a solution to this problem. With respect to this it is known that spine size and shape change as a result of actin filament changes. Actin filaments transmit signals to subsynaptic microtubules linked to other microtubules by MAP2. The authors advance the notion that memory could be stored in the cytoskeleton just below the dendritic spine putting it in an optimum position to respond to new input. Actin filaments in the spine are seen as linking to microtubules in the main part of the dendrites, and changes in microtubules and MAP2 are also related to learning. The transport of RNA, cytoskeletal and scaffolding proteins and receptors are all related to the reorganisation of dendritic spines seen in learning and memory. Some attempts to build quantum computers using a combination of Buckminster fullerenes and artificial carbon nanotubes have tried to utilise dipole interactions of the kind that are available in microtubules. It is suggested that the lattice arrangement of the tubulin could allow coherent coupling between the tubulins. The organisation of tryptophan and histidine amino acids within tubulin creates helical conduction routes, and elsewhere it is claimed that the arrangement of tryptophan resemblances the quantum coherent arrangements in photosynthetic light harvesting. The authors argue that some brain processing is better suited to quantum superposition than to classical processing. The matrix of current sensory input, past experience stored in memory, future expectations and underlying mood could be thought to be a superimposition of different possibilities, rather than the outcome of classical calculation. P. The disappointing aspect of this book is its failure to discuss the implications of recent studies demonstrating that quantum coherence is functional in photosynthetic biological organisms even at room temperature. The last part of the book which touches on quantum consciousness appears rather muddled. This is despite the fact that Travis Craddock, mentioned in the preface with respect to double wells in tubulin, points out that the arrangement of the amino acid tryptophan in tubulin bears a resemblance to the quantum coherent structures in photosynthetic organisms. The type of quantum coherence found in these organisms might point to a more slim line structure than the model developed over many years by Hameroff. It would have been valuable to have had a full discussion on these issues. |
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