S. Murray Sherman

Maurice Goldblatt Professor and Chairman,

Department of Neurobiology

The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637

Email: msherman@bsd.uchicago.edu
Phone: (773) 834- 2900
Office: Abbott 316 (MC 0926)

Sherman Lab website

Research Summary

Thalamic functional organization

Research Statement

The research in the laboratory is 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.

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.

We are now exploring for glutamatergic pathways in cortex whether this driver/modulator distinction holds, and it so far does appear to, providing a much-needed classification of glutamatergic circuits.

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. Other possible roles are also under study.

Select Publications

Theyel, B.B., Llano, D.A., and Sherman, S.M. (2010) The corticothalamocortical circuit drives higher-order cortex. Nat. Neurosci., 13, 84-88.

Lee, C.C., and Sherman, S.M. (2010) Topography and physiology of ascending streams in the auditory tectothalamic pathway. Proc. Nat. Acad. Sci., 107, 372-377.

Llano, D.A., Theyel, B.B., Mallik, A.K., Sherman, S.M., and Issa, N.P. (2009) Rapid and sensitive mapping of long range connections in vitro using flavoprotein autofluorescence imaging combined with laser photostimulation. J.Neurophysiol., 101, 3325-3340.

Lee, C.C., and Sherman, S.M. (2008) Synaptic properties of thalamic and intracortical inputs to layer 4 of the first- and higher-order cortical areas in the auditory and somatosensory systems. J. Neurophysiol., 100, 317-326.

Sherman, S.M. (2007) The thalamus is more than just a relay, Current Opinion in Neurobiology, 17, 417-422.

Sherman, S.M , and. Guillery, R.W. (2006) Exploring the Thalamus and its Role in Cortical Function. MIT Press, Cambridge, MA.

Guillery, R.W., and Sherman, S.M. (2002) Thalamic relay functions and their role in corticocortical communication: Generalizations from the visual system, Neuron, 33, 1-20.