Triadic synaptic interactions of large corticothalamic terminals in non-lemniscal thalamic nuclei of the cat auditory system

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Abstract

Large corticothalamic (CT) terminals, presumed to originate from cortical layer 5 pyramidal cells, are distributed predominantly in non-specific thalamic nuclei in mammals. In the auditory system, little is known about whether these CT projections participate in the synaptic aggregation referred to as the triad. We studied synaptic interactions of these terminals with neuronal elements in one of the auditory non-lemniscal thalamic nuclei, the dorsal nucleus of the medial geniculate complex (MGC), in cats. After injections of an anterograde tracer in the primary auditory cortex, areas containing labeled large terminals were examined using an electron microscope. It was revealed that a fraction of large CT terminals participated in complicated synaptic arrangements: labeled terminals making synaptic contacts with vesicle-free dendrites, probably of thalamic principal neurons, and/or vesicle-filled neuronal profiles, probably of presynaptic dendrites (PSDs) of interneurons. In reconstructions or even in single sections, we found that these synaptic connections participated in triadic arrangements. Thus, PSDs postsynaptic to the labeled CT terminals were in turn presynaptic to the vesicle-free dendrites.

Introduction

The classical view of the role of the thalamus is currently changing (see Jones, 2007 for review). It is becoming increasingly important to consider that the thalamus is not only a relay station transferring sensory information from the periphery to the cortex, but also receives information already processed in cortical areas and transmits it to adjacent cortical areas that are higher in the hierarchical progression (Guillery, 1995). This transthalamic pathway is mediated by descending axons of cortical layer 5 pyramidal neurons (Ojima, 1994, Bourassa et al., 1995, Bourassa and Deschênes, 1995). It is different from the traditional corticothalamic (CT) projection that originates from layer 6 and terminates chiefly on distal parts of thalamic relay neurons (Guillery, 1969, Jones and Powell, 1969b). Thus, the cortex has two components in terms of projection to the thalamus. In a simplified scheme, with primary sensory cortex as an example of an area containing cells of origin, small domains in each primary sensory cortex project back to the corresponding principal (or specific) thalamic nucleus, with axons originating in layer 6, and to non-specific thalamic nuclei with axons originating in layer 5. In the former, reciprocal projections between cortex and thalamus are well preserved, but this is not the case in the latter (Van Horn and Sherman, 2004, Llano and Sherman, 2008; but see Huppé-Gourgues et al., 2006). Consequently, as a whole, the entire CT projection originating from a single cortical locus ends in thalamic nuclei in a divergent manner (Guillery et al., 2001, Winer et al., 2001).

Target thalamic nuclei of large CT terminals include almost all non-principal nuclei (see Rouiller and Welker, 2000 for review), such as the pulvinar and lateral-posterior nucleus in the visual system, the posterior nucleus in the somatosensory system, the dorsal nucleus of the medial geniculate complex (dMGC) in the auditory system, and others. The morphological characteristics of the two distinct types of descending CT projections have been characterized by terminal size, aggregation pattern of multiple terminals, and the extent of their distribution in major sensory systems of various animal species (Robson and Hall, 1977, Ogren and Hendrickson, 1979, Hoogland et al., 1987, Rouiller and de Ribaupierre, 1990, Rouiller and Welker, 1991, Rouiller et al., 1991, Kuroda et al., 1993, Ojima, 1994, Rockland, 1994, Bourassa and Deschênes, 1995, Bourassa et al., 1995, Bajo et al., 1995, Vidnyánszky et al., 1996, Ojima et al., 1996; Winer et al., 1999, Guillery et al., 2001, Li et al., 2003b, Rouiller and Durif, 2004, Hazama et al., 2004, Kimura et al., 2005, Zikopoulos and Barbas, 2006), and also for the motor system (Rouiller et al., 1998, Kakei et al., 2001).

Findings that layer 5-derived CT terminals are larger than layer 6-derived CT terminals have been confirmed in most cortical areas in many animal species. Large CT terminals occasionally end with the clustering of multiple boutons, giving an impression of a “bunch of grapes” in cats (see Fig. 5 of Ojima, 1994 as example), or they end in giant swellings in rodents (Hoogland et al., 1987, Hoogland et al., 1991, Bartlett et al., 2000, Li et al., 2003b) and monkey (Rouiller et al., 1998), occasionally forming aggregations connected by a short axon.

The ultrastructure of the large CT terminals has been investigated with special reference to their resemblance to sensory ascending afferents and the complexity of synaptic formations they made. Sensory afferents projecting to thalamus from the periphery, for example, the retina and trigeminal nucleus (Szentágothai, 1963, Guillery, 1969, Jones and Powell, 1969a) end with terminal boutons that participate in distinct synaptic interactions. These involve, in cat and monkey, three elements: presynaptic dendrites (PSDs) in interneurons, an afferent terminal, and dendrite(s) of thalamic principal neurons. The synaptic arrangement formed by these elements is traditionally referred to as a triadic arrangement, synaptic aggregation, or glomerulus if they are encapsulated together by glial lamellae (see Jones, 2007 for review). It is proposed that large CT terminals derived from layer 5, despite descending in the direction of the projection, form synaptic arrangements similar to those found for ascending sensory afferents in primary cortices (Hoogland et al., 1991, Schwartz et al., 1991, Vidnyánszky et al., 1996, Feig and Harting, 1998: Van Horn and Sherman, 2004).

In the auditory system, ultrastructural studies have been limited to rats (Bartlett et al., 2000). Reconstructions from serial sections have not been done. Since the rodent is characterized by very rare occurrences of GABAergic interneurons in the sensory thalamus (with the exception of the dorsal lateral geniculate nucleus) (Thompson et al., 1985, Winer and Larue, 1988, Winer and Larue, 1996, Arcelli et al., 1997), triadic synaptic arrangements would not be expected in the auditory thalamus. Indeed, it was shown that large CT terminals do not form triad–like synaptic interactions in the rat. Their (exclusive) targets in the rat dMGC are the dendrites of principal neurons, although these are occasionally enwrapped partially by glial sheaths. Thus, it is still not known if large CT terminals are involved in triadic synaptic arrangements in the auditory thalamus of non-rodent species. This has been shown in other sensory systems. In this report we examined the synaptic organization of non-lemniscal large CT terminals grouped in small clusters that were not contaminated by small, drumstick-like shaped terminals derived from, presumably, layer 6 CT axons. Some of the labeled large CT terminals were subjected to reconstruction from serial sections.

Section snippets

Animals

Two cats (male; 3.4 and 4.0 kg; Saitama Experimental Animal) were used for electron microscopic examination. In addition, light microscopy drawings (see Fig. 1a) were obtained from serial sections used previously to reconstruct 3 dimensional distributions of CT terminals across the cat MGC (Takayanagi and Ojima, 2006). Animals were subjected to surgery and care under the approval of the Animal Care Committee of Toho University, in accordance with the National Institutes of Health Guide for the

Observation of labeling using light microscopy

Distribution and light microscopy images of small and large CT terminals revealed by labeling cells of origin in the cat AI (Fig. 1) were consistent with those described previously for the auditory cortex (Rouiller and Welker, 1991, Bajo et al., 1995, Llano and Sherman, 2008), and were also similar to those described for other sensory and motor cortices. The differential projections of small and large CT terminals, known to be derived from layers 6 and 5 pyramidal neurons, respectively, were

Discussion

Our study has two major strengths that convince us of the validity of our interpretation of the synaptic organization of large CT terminals projecting to the non-lemniscal auditory thalamic nucleus. First, samples used for observation using an electron microscope contained only large terminals or clusters of large terminals. This was made possible by trimming out small areas of the dMGC that contained exclusively large terminals and had no contamination of small, drumstick-like terminals

Ackowledgements

Through our continuous conversation exchanged during the Society for Neuroscience and ARO meetings, Jeff and I came to agree that the large terminals projecting back from the auditory cortex to the non-lemniscal MGC deserved more careful study. It is common in anatomy that it is within the visual system that new, crucial connections are found. However, the direct visualization of this peculiar CT projection ending with large terminals, frequently forming clusters, in non-specific thalamic

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