The research in the laboratory is all directed at issues of thalamic functional organization and thalamocortical relationships. We use a broad interdisciplinary approach, attempting to answer the same or closely related questions with several different techniques. These involve neuroanatomical, neurophysiological, and behavioral methods. More specifically, we use light and electron microscopic techniques to explore various circuits; we use in vitro recordings from brain slices to study cell and synaptic properties; and we record from single thalamic neurons in awake, behaving animals to determine the relationship between behavioral state and thalamic functioning.
Burst and tonic firing modes
All thalamic relay cells can fire in one of two modes -tonic and burst- depending on the inactivation state of a voltage gated Ca-2+ current. This current is based on T-type Ca-2+ channels found in the dendrites and soma, and thus the inward Ca-2+ current that flows through these channels when they open is called I-T. These channels are inactivated at depolarized membrane potentials, but this inactivation is removed at membrane potentials more hyperpolarized than about -70 mV (i.e., they are then de-inactivated). Once de-inactivated, they can be activated by a suitably large depolarization, such as a retinal EPSP, and activation leads to I-T. This, in turn, leads to an autocatalytic, all-or-none response, like a conventional action potential, except that here is a Ca-2+ spike that propagates through the dendritic arbor. This is called the low threshold spike, because it activates from a more hyperpolarized level than the conventional action potential, and riding its crest is a high frequency cluster of typically 3-6 action potentials. This is the burst firing mode and is present when a relay cell is activated from a relatively hyperpolarized level. The tonic firing mode occurs when the same cell is activated from a more depolarized level (e.g., more than about -60 mV), and here the T-channels are inactivated and thus play no role in the response, which is in the form of a stream of unitary action potentials that last as long as the activating stimulus is superthreshold.
Thus burst and tonic firing modes represent two different signals relayed to cortex in response to the same stimulus (e.g., a retinal input), and this difference reflects the recent voltage history of the relay cell. We have suggested that tonic firing mode, which is more linear, is better for faithful reconstruction of the external signal (i.e., the visual stimulus for a geniculate relay cell). Burst mode, which is highly nonlinear, is better for signal detection as a sort of "wake-up call", both because it represents a higher signal-to-noise ratio and also because it produces a stronger postsynaptic response in cortex. Both firing modes are seen in awake behaving animals, but the more alert the animal, the more tonic firing dominates.
Our experiments are directed at understanding more of the properties of the T-channels in relay cells, how they are controlled by thalamic circuitry, and how behavioral state, including various types of attention, relate to burst or tonic firing.
Drivers and modulators
We have pointed out that not all afferents to thalamic relay cells are equal, and that it is important to identify which input carries the information to be relayed. Examples are the retinal input to the lateral geniculate nucleus and medial lemniscal input to the ventral posterior lateral nucleus. These we call the driver inputs. All other inputs, such as those from layer 6 of cortex and the midbrain, are modulator inputs and determine how driver inputs are relayed. Included in this modulatory role is the control of firing mode and its switching between tonic and burst. We have generated a list of features that distinguish drivers from modulators and have further suggested that this duality of inputs types might be applied to other pathways, such as those in cortex.
First and higher order relays
Because driver input determines the nature of a thalamic relay (i.e., the lateral geniculate nucleus is a visual relay because it relays retinal input), identifying the driver input to a thalamic relay is a key first step in understanding its function. In the process of doing so, we realized that the driver input to many thalamic relays originate in layer 5 of cortex. This is different from the corticothalamic pathway emanating from layer 6: all thalamic relays receive a layer 6 input, and this is largely feedback, while only some receive an additional layer 5 input, and this is feedforward. Thus those with layer 5 input are the thalamic limb of a cortico-thalamo-cortical pathway, being a key link in a chain of corticocortical communication.
Those thalamic relays receiving driver input from the periphery are first order relays, because the represent the first relay of peripheral information to cortex. Those that receive a driver input from layer 5 of one cortical area and relay it to another are higher order relays, because they relay information already in cortex between areas. Examples of first order relays for vision, somesthesis, and hearing are the lateral geniculate nucleus, the ventral posterior nucleus, and the ventral part of the medial geniculate nucleus; their higher order partners are the pulvinar, posterior nucleus, and magnocellular part of the medial geniculate nucleus. We have also identified other first and higher order relays, and it appears that most of thalamus is higher order.
This idea that higher order relays play a key role in corticocortical communication challenges the dogma that this communication is largely the result of direct corticocortical connections. We have suggested that many of these, and perhaps all, are modulators and thus do not actually carry information. We suggest a major challenge is to determine which corticocortical pathways are drivers and how these relate to the higher order thalamic relays and cortico-thalamo-cortical circuits for information processing in cortex.
Thalamic relays as a corollary of motor commands
We have noted that many and perhaps all driver inputs are branches of axons that also project to motor centers. Thus, for example, many or all retinal axons innervating the lateral geniculate nucleus branch to also innervate midbrain centers involved in the control of eye movements or pupil size. Also, the cortical layer 5 axons innervating higher order thalamic relays branch to innervate brainstem motor regions and sometimes even the spinal cord. We are thus considering the idea that thalamus relays corollary information about motor commands, and that the role of cortico-thalamo-cortical circuits is to continuously upgrade these commands and simultaneously inform higher order cortical areas of this.
