Thalamic Circuit Diversity: Modulation of the Driver/Modulator Framework

Abstract

The idea that dorsal thalamic inputs can be divided into "drivers", which provide the primary excitatory drive for the relay of information to cortex, and "modulators", which alter the gain of signal transmission, has provided a valuable organizing principle for the study of thalamic function. This view further promoted the identification of "first order" and "higher order" thalamic nuclei, based on the origin of their driving inputs. Since the introduction of this influential terminology, a number of studies have revealed the existence of a wide variety of thalamic organizational schemes. For example, some thalamic nuclei are not innervated by typical driver inputs, but instead receive input from terminals which exhibit features distinct from those of either classic drivers or modulators. In addition, many thalamic nuclei contain unique combinations of convergent first order, higher order, and/or other "driver-like" inputs that do not conform with the driver/modulator framework. The assortment of synaptic arrangements identified in the thalamus are reviewed and discussed from the perspective that this organizational diversity can dramatically increase the computational capabilities of the thalamus, reflecting its essential roles in sensory, motor, and sensory-motor circuits.

Keywords: corticothalamic; dorsal lateral geniculate nucleus; lateral posterior nucleus; pulvinar nucleus; retinogeniculate; tectothalamic; thalamocortical.

Figure 1

Synaptic terminal types in the dorsal thalamus defined using electron microscopy. Electron microscopic images of the cat dorsal lateral geniculate nucleus (dLGN) are shown. Tissue was obtained from a previous study (Bickford et al., 2008); postembedding immunocytochemical techniques were used to reveal the presence of gamma amino butyric acid, GABA, with gold particles). (A) A dLGN glomerulus is illustrated which contains a large profile with round vesicles (RL, green), GABAergic dendritic terminals (F2, yellow, high density of gold particles), and relay cell dendrites (blue). A GABAergic axon terminal (F1, purple, high density of gold particles) is located at the periphery of the glomerulus. The asterisk indicates the location of a synapse shown at higher magnification in (B). (B) The arrow indicates a synaptic contact of the RL profile (green) onto a relay cell dendrite (blue). (C) A non-glomerular region of the dLGN is illustrated which contains small profiles with round vesicles (RS, pink) that synapse on relay cell dendrites (blue). The asterisk indicates the location of a synapse shown at higher magnification in (D). (D) The arrow indicates the synaptic contact of an RS profile (pink) onto a relay cell dendrite (blue). Scale in (A) = 2 μm and also applies to (C). Scale in (B) = 0.5 μm and also applies to (D).

Figure 2

Schematic summary of synaptic terminals types and their arrangements in the dorsal thalamus. Class I axons (Guillery, 1966) form small terminals with round vesicles (RS; Guillery, 1969) that are defined as modulators (Sherman and Guillery, 1998). RS terminals that originate from cortex layer VI converge on small caliber (distal) dendrites (depicted by the gray terminals surrounding a section of dendrite, pink, modified from Robson and Hall, 1977). Repetitive stimulation of layer VI corticothalamic terminals results in a frequency-dependent facilitation of excitatory postsynaptic potentials (EPSPs; depicted by gray traces, from Li et al., 2003a). Class II axons (Guillery, 1966) form large terminals that contain round vesicles (RL; Guillery, 1969) that are defined as drivers (Sherman and Guillery, 1998). RL terminals that originate from the retina, medial or lateral lemniscus, or cortex layer V, form relatively few synapses on large caliber (proximal) dendrites (depicted by the red terminals surrounding a section of dendrite, pink). Repetitive stimulation of RL terminals results in a frequency-dependent depression of excitatory postsynaptic potentials (depicted by red traces, from Li et al., 2003a). Class III terminals form medium size terminals that contain round vesicles (RM; Robson and Hall, 1977), here refered to as “driver-like”. RM terminals that originate from the superior colliculus (tectal) converge on large caliber (proximal) dendrites (depicted by the blue terminals surrounding a section of dendrite, pink, modified from Robson and Hall, 1977). Repetitive stimulation of tectothalamic terminals results in little change in the amplitude of EPSPs (depicted by blue traces, from Masterson et al., 2010). First order nuclei (red neuron, modified from Bickford et al., 2015) receive a small number of RL inputs on their proximal dendrites that originate from a single subcortical source (red terminal). Higher order nuclei (yellow neuron) receive a small number of RL inputs on their proximal dendrites that originate from cortex layer V (yellow terminal). Tectorecipient nuclei (dark blue neuron) receive convergent RM inputs on their proximal dendrites (light blue terminals). As discussed in the text, a variety of combinations of first order, higher order and tectal inputs have been identified which may result in emergent receptive field properties (depicted by the orange, purple and green neurons).