Pathways to Consciousness

Some Basics of Thalamocortical Signaling, and Highlights of Edward Jones’ Recent Theoretical Reorganization of the Corticothalamic Axis

The two thalami are the gateways to the cerebral cortex and, thus, to consciousness. Like almost all major brain structures the thalami are bilateral or paired structures. These two walnut-sized globes are comprised of about 50 grouping of nerve cells, neural tissue, and fibers called nuclei. They are located just under the two brain hemispheres which they serve.

The thalamus has often been called “The Switchboard of the Brain.” As brain scientists have studied it in more detail, they have learned how much more it is than just a switchboard. An updated 21st Century metaphor for the thalamus might be the brain’s “Adaptive, Cybernetic, Computing, Selecting, and Switching Center.”

The thalamic nuclei specialize in several different signaling functions:

1. Transmitting signals from sensory input, like the eye, to the cortex.
2. Transmitting signals from cortical motor centers to effectors, like the fingers I am using to type this sentence.
3. Transmitting control signals that select which input and output will be permitted to pass to and from the cortex and how the signals will be sequenced. The Thalamic Reticular Nuclei (TNR), discussed below, play a major role in this function.
4. Modulating (controlling intensity) and synchronizing (grouping) the signal traffic. The Intralaminar Nuclei (ILN) of the thalamus, briefly discussed below, play a major role in this function. In fact, the functions of the ILN are so critical for consciousness that cutting the nerve fibers of some of them results in coma and unconsciousness!

Total loss of consciousness only occurs with damage to a few regions, like the ILN and the brainstem. In contrast, injury to other brain structures can change consciousness other ways, like impairing a sense like hearing, blocking certain types of movement like head motion or causing temporary or permanent loss of memories.

The Thalamic Reticular Nucleus (TRN)

The TRN looks like a thin skin over part of the thalamus. It contains inhibitory neurons that connect to most of the large nuclei thalamus. In return, all thalamic nuclei and areas of the cortex can transmit to the TRN. (Guillery and Harting, 2003). It is the hub of the hub.

Neighboring neurons of the TRN inhibit each other, what brain scientists call ‘lateral inhibition’. Lateral inhibition helps to sharpen the border between excitation and inhibition when relay neurons transmit their signals through the TRN. That type of excitatory-inhibitory pattern is called a center-surround field. A small central area is excitatory, and an inhibitory zone completely surrounds the excitatory center. When you touch your forearm with the tip of your finger, you are creating a center-surround field in several cortical maps that receive signals from the skin.

All thalamic relay neurons pass through the TRN, which opens and closes their “gates” going to the cortex, like a traffic cop (McAlonan and Brown, 2002). One mode of TRN neurons is called the “burst firing” mode, like a squirt gun. That mode is useful for activating a small population of neurons in cortex for a short period. For example, when you hear your alarm clock in the morning, thalamic neurons are arousing your cortex for a moment. But you might shut the alarm off and fall right back to sleep and unconsciousness.

In contrast, the continuous (tonic) firing mode permits a thalamic neuron to transmit a steady stream of signals to the cortex. The tonic firing pattern triggers looping activation in the cortical circuits that receive the signals. Evoking looping, or “recurrent” activation in the cortex requires a steady neural input. This is more like a friend who keeps shaking you and calling your name to wake you up, rather than letting you fall asleep again.

Signals from the following sources can change the state of the thalamus.

1. Signals from senses that are relayed by thalamus to cortex (e.g., from the eyes).
2. Signals from the cortex.
3. Signals from the ILN of the thalamus (see below).
4. Signals from the brainstem Reticular Activating System. The most important brainstem nuclei and their primary neural messengers are: the raphe nucleus (serotonin), the locus ceruleus (norepinephrine), pedunculopontine nucleus (acetylcholine) and the substantia nigra compacta (dopamine).

Since the thalamus is the great hub on the highways of the senses and motor systems – coming from the world to the cortex, and going back — we will talk about neurons that go from thalamus to cortex as “T-C” neurons. (“thalamo-cortical”). When they go the other way, they are “C-T” neurons. And when a pathway starts in cortex, bounces down to the thalamus, and then comes back to cortex, it would be “C-T-C”. Like a traffic hub, you might drive your car to the main square in town, and then go to your destination. The thalamus is a place where many pathways come together, with stop and go traffic lights controlled by the TRN.

Intralaminar Nuclei (ILN)

The ILN are a tiny cluster of cells in central body of the thalamus, hidden inside of the “laminae,” the white layers that separate the bigger nuclei of the thalamus. Although they are small, they are very powerful.

There are about ten ILN in each thalamus. In contrast to the bigger relay nuclei, which send signals from senses like the eyes, most of the ILN send signals that change the activity of the cortical receiving area (Sherman and Guillery, 2002). Most of the large relay nuclei are neatly mapped on the sensory input — the visual field, for example. That is, they are topographically organized 1. But the ILN projections to cortex may not be topographically mapped. Instead, they influence the traffic flow on the big highways going to cortex.

For example, an ILN might receive signals from one cortical area and send them on to several other cortical areas to increase excitation in the receiving areas (a cortico-thalamo-cortical pattern, C-T-C). A C-T-C signal might excite several senses all together, as when an rabbit is chased by a fox. Getting information from all the senses maximizes the information available to the rabbit for sensing and running away from the fox.

Ed. Note: Currently these regions of the brain are receiving intense study. SCR will report progress in this area of consciousness-related science in future articles. This article is focused on Edward Jones’ research and his theory of ILN signaling.

A Thalamocortical Theory

Edward G. Jones has studied thalamic systems over three decades. Jones authored and edited two of the best-known works on this vital region of the brain. His most recent work, “The Thalamus”, was published in 1997 in two volumes. Currently, Jones heads the Neuroscience Center at University of California, Davis. http://web.archive.org/web/20040603120037/http://www.dbs.ucdavis.edu/neuro/faculty/?EJones

More recently Jones introduced a new theory of thalamocortical signaling. This major new approach involves a molecule-tagged analysis of T-C neurons (Jones, 1998). It suggests a new classification goes beyond the traditional one that is based on the thalamic relay nuclei, the major highways to the cortex. This new approach is based on neurons that are ‘tagged” with two different molecules, either parvalbumin (an egg-derived protein) or calbindin (a calcium-binding protein) (Jones, 2002b).

Calcium-binding proteins are involved in specific neurotransmitters called second-messengers 2, chemicals that serve to connect two neurons to each other. Second-messengers can trigger spikes — messages that travel along neuronal fibers. They can also modify the workings of the cell. Such processes have been associated with learning. Being able to chemically tag these messengers is therefore vital.

Jones contrasts a “core” of parvalbumin-binding neurons with an embedding “matrix” of calbindin-binding neurons. Core neurons generally include relay cells, which are usually topographically organized. That is, they might map a single point in the senses into a corresponding region in cortex. In contrast, matrix neurons generally include second-order relay neurons and associated ILN cells (see above). Signals sent by these neurons typically modify other neurons.

According to Jones, perceptual binding — an essential ingredient in conscious perception — happens when matrix neurons are recruited by output from the fifth layer of the cortex going back down to the thalamus (C-T). Matrix neurons are generally triggered during a second cycle, i.e., from the cortex to the thalamus and back to the cortex again (C-T-C). On Dr. David McCormick’s lab website at Yale you can see video clips of some thalamic cells firing.

Matrix elements signal embedding fields. These fields are related to specific primary sensory signal sets that form the dominant focus of sensory attention.

Interneurons of thalamic reticular nuclei (TRN) are color coded in yellow on diagram below. The dorsal thalamus (which includes the principal sensory nuclei) is covered with thin, skin-like neural tissue comprised of patches of inhibitory interneurons. The interneurons of this skin normally provide tonic (continuous) inhibition of first-order or sensory relay neurons. These interneurons are themselves phasically (briefly) inhibited or tonically inhibited to permit thalamic relay neuron signals to be transmitted to the cortex. This characteristic of being “normally inhibited” prevents signal overload due to chaotic firing of all relays at once.

Blue – Output signals from sensors like the eyes and ears. These are first-order thalamic relay neurons, carrying the signals from sensor networks (most are parvalbumin-binding).

Cortex Layer IV – Input to the cortex

Center Black Object – A pyramidal neuron; the principal excitatory neuron in the cortex, triangle symbol is for the cell body.

Cortex Layer V goes to the brainstem, branching off from the connection to thalamus.

Cortex Layer VI outputs to the thalamic reticular nucleus, which enhances center-surround sharpening by inhibiting areas all around the main activity.

Purple – Second-order relay neurons do not carry output from the senses like the eye (Matrix, ILN; most of these are calbindin binding).

The purple also contains horizontal branching processes. Cortex Layer I contains perceptual binding and synchrony processes which can spread over the borders of traditional cortical areas. They trigger second-messenger neurotransmitters. Layer I contains input fibers from several other cortical layers.

Figure 1: A Typical Thalamus-Cortex Signaling Sequence

(after Jones)

Figure 1: Coincidence detection 3 of “core” and “matric” T-C activity. Inputs from core and matrix cells oscillating at high frequencies (~40hz) would be integrated over input fibers (dendrites) and promote spikes in these cells. Feedback from Layer VI C-T cells would further promote such activity. The wide spread of matrix cell endings in cortex and Layer V C-T connections would also synchronize separate regions of cortex and thalamus. From Jones (2001b), based in part on Llinas and Paré (1997). Used with permission.

Some Ways Jones’ Theory Might Apply to Understanding Consciousness

Jones’ molecular discovery of “core” and “matrix” neurons suggests synchronization of co-active pathways via short-term inhibition. The basic idea is to time the activation of wave signals to increase the chance that they will produce a phase pattern (somewhat like a motion picture) combining different types of signals the waves are carrying. For theories of phase-based signaling, see Izhikevich’s website.

Core and matrix cells could synchronize two global waves or rhythms with different time constants. For example, the neurons controlling a C-T wave would be released from inhibition a few milliseconds after the T-C wave is released. Controlled timing such as this would insure that the waves would interact. One cycle of perception could involve both C-T and T-C waves acting in sequence.

One wave could synchronize T-C signals by rebound from inhibition (Huguenard, 1998). This is a timing control process which delays excitation in a group of neurons that are not firing in synchrony. After the delay the neurons can begin firing at the same time when excitation recurs. The other wave could synchronize C-T signals (Ahissar et. al, 1997).

FM radio also works this way. Phase-locked loops in electronic circuits are used to maintain precise tuning. Control signals adjust the tuning of the FM receiver if it drifts from the exact broadcast frequency. A comparator circuit with the desired frequency locks onto the FM broadcast signal and prevents the signal from drifting. For more on phase-locked loops, see the tutorial at: http://www.uoguelph.ca/~antoon/gadgets/pll/pll.html

As a side benefit, this mechanism could prevent neurons from being poisoned by too much calcium. Calcium is needed to release neurotransmitter into the synapse, the gap between two neurons. In two firing cycles — 50 milliseconds — calcium could be released and hustled away to a safer part of the system.

Several types of glutamate receptors, both fast-acting and slower-acting, are involved in the primary or driving signaling which carries the neural signaling code. Both dopamine and serotonin 4 are likely candidate neuromodulators for tuning and shaping the two interacting global waves. Neuromodulators can modulate the intensity of the neural signal stream, in contrast to neurotransmitters, which carry the patterned neural code. (Moore, 1993)

For another wave theory of consciousness see LaBerge (2002). In LaBerge’s model, waves are transmitted from one or more output cortical Layer V’s to the apical dendrites in layer 2/3 and Layer 1. This neural action underlies the current oscillations measured as EEG.

A second wave carries control signals which will trigger sensory patterns in posterior cortices. The signals will be focused on the basal dendrites of some of the neurons whose apical dendrite were also stimulated during the unfolding of this consciousness epoch. LaBerge carefully distinguishes between sensory controllers (which modulate attention) and the information fields or patterns (which comprise the output selected and controlled). The interaction of the two waves generates patterns for on-going epochs of consciousness.

© 2004 Gene Johnson

Author Information

Gene Johnson, Ph.D. (ABD)
Brain-Behavioral Scientist, Consultant
Charlottesville, VA 22901

E-mail: gjohnson3rdnospam@earthlink.net (remove nospam)

Footnotes

1. Topographic organization = a point-to-point map, just like a geographical map that shows a land region. The size of terrain features and symbols on the map are different than the reality they represent.
2. Second messengers = Molecular processes inside the neuron which can control neuronal firing or readiness to rapidly fire again. Also second messengers can send signals to the cell nucleus which can change cellular metabolism and structure. These latter changes can affect synaptic connection strengths among neurons, thereby controlling learning and memory.
3. Coincidence detection. Activation goes to a neuron’s input fibers near the cell body AND to its output fibers in less than 25 milliseconds. The combined action of the two signals can trigger a spike — a large, all-or-none impulse. This coincidence of two signals may explain the “40 Hz phenomenon,” and its association with conscious processes.
4. Dopamine and serotonin neurochemical systems can modulate a number of neuronal groups together. These systems often dynamically oppose one another to maintain global or wide-spread balance among excitatory and inhibitory signaling processes related to sustained consciousness. For more info, see this link for a collection of excellent tutorials on neuromodulators and neurotransmitters:

References

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