Attention is a deliberate action whereby one directs conscious operations to a particular sensory stimulus, to a memory, or to a complex amalgam of both stimulus and memory. Sensation, attention and arousal are mediated through different neurotransmitter pathways, each of which will affect brain microtubules in different ways.
Glutamate neurotransmission transmits sensory data all along the sensory pathways. A sensory pathway begins in a sensory organ (i. e. the retina, cochlea, vestibular organ, skin, taste buds or nasal epithelium), usually makes synaptic contact in the thalamus, then relays to a primary sensory cortex, and then through a series of corticocortical circuits reaches higher association cortex. The glutamate system is topographically organized (e.g., visuo-topic, tonotopic or somatotopic) such that the location of the visual field, the cochlea, or the body onto which stimuli are mapped is preserved at each relay. The sensory systems organize information from external sources in a point-to-point scheme. By analogy, it is like every person living in New York City being in phone or email contact with one person in Los Angeles who lives at the same north-south and east-west placement in the corresponding city. This system is "online"; new information is continually coming in.
Global systems of neurons utilize the neurotransmitters acetylcholine and monoamines: norepinephrine, serotonin and dopamine38. These cellular aggregates receive sensory collateral branches from axons en route to the cere
36 Memory is related to oscillations in the theta and gamma range, whereas attention is related to alpha and gamma .
37 Memory that reaches consciousness is called explicit or declarative.
38 These groups of neurons form interconnected cellular aggregates throughout the hindbrain and basal forebrain enabling a high degree of crosstalk between constituent neurons .
bral cortex. In this manner, these neurons obtain a general idea of the overall pattern of incoming inputs and then base their outputs on those assessments. Cholinergic systems contribute to selective attention, whereas nore-pineprhine, serotonin and dopamine systems contribute to general arousal or vigilance. Cholinergic neurons from the basal forebrain are able to contribute to selective attention because they innervate discrete areas of cortex of a single modality measuring 1-2 mm2 . Noradrenergic, serotonergic and dopamine neurons in the brainstem innervate the cortex less restrictively. A single no-radrenergic fiber, for example, may provide inputs to many different types of cortex, as these fibers are long and have many release sites along their paths.
Taking into consideration that attention is a deliberate act, what neuro-chemical component of the neural circuit could be responsible for it? The glu-tamatergic synapse per se cannot be the source of attention. Sensory inputs in some cases do reach consciousness, but often they do not reach consciousness. What part of the glutamate synapse would decide, and on what basis? These synapses are passive, responding to inputs. Even in the presence of enhanced synaptic efficacy (e.g., LTP), how would such potentiation lead to attention and consciousness? Going back to the analogy of one person in New York City being in direct contact with one similarly placed person in Los Angeles, we might view increased synaptic efficacy as an increase in information flow between selected persons in this one-to-one connected network. Would selectively increasing information flow attain an increased level of attention or reach consciousness? No, not in this one-to-one connected network, which is not too far from the way cortical systems are organized. A mechanism is needed that accesses the overall pattern of inputs and compares these patterns to input patterns occurring in the remembered past and input patterns anticipated in the future.
Cholinergic and monoaminergic inputs seem closer candidates for this role of accessing the overall pattern of inputs, insofar as these systems sample sensory activity en route to the cerebral cortex. On the other hand, the information these systems relay cannot be precise enough, since their terminal fields are diffusely distributed to cortical modules or to the entire cortex. These inputs are necessary, but not sufficient for attention and arousal. Activation by glutamate, acetylcholine and norepinephrine are obligatory steps for a stimulus to receive attention. But all these synapses are passive; none has the "actor" status needed to decide whether to deliberately arouse consciousness or to select content.
Self-organizing microtubule networks inside dendrites do have the "actor" status needed to deliberately direct attention and consciousness. Because mi-crotubules can polymerize and depolymerize, they can search for and activate particular subsynaptic sites. Although release of glutamate, acetylcholine and monoamines is obligatory for full conscious awareness, this behavioral state must also rely on the biophysical state of the microtubule network. Just as phosphorylation of MAP2 and its subsequent binding can affect the biophys ical state of the microtubule, the biophysical state of the microtubule can affect the binding of MAP2. As a specific example, the biophysical state of the microtubule can induce the release PKA through effects on the regulatory subunit RII^ of PKA. Bidirectional effects on PKA-mediated transphospho-rylation of neighboring MAP2 causes the "zipping" and "unzipping" between neighboring microtubules, leading to subsequent increases and decreases in the rate of kinesin-mediated transport along microtubules39. Regulation of transport is necessary to maintain large spines, which are laden with many AMPA receptors.
These, among other effects, would enable the microtubule network to direct attention and consciousness. Accordingly, the psychical sensation of attention could not possibly be associated with synaptic activity per se, since those activities occur both in the presence and in the absence of attention. Instead, the psychical sensation of directed attention and consciousness could well be associated with the biophysical state of microtubules that regulates (1) polymerization and depolymerization cycles linking synapses and (2) transport to active synapses.
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