Cellular architecture of the nucleus reuniens thalami and its putative aspartatergic/glutamatergic projection to the hippocampus and medial septum in the rat

Abstract

Little is known about the neurochemical features of the nucleus reuniens thalami (RE). In the present study, immunocytochemical experiments were performed to characterize the expression pattern of certain neurochemical markers, e.g. the calcium-binding proteins calbindin and calretinin and several neuropeptides. Colocalization studies revealed that half of the calbindin-positive cells express calretinin, and numerous calretinin-immunoreactive neurons contain calbindin. In contrast, immunolabelling for neuropeptides did not reveal cell bodies in the RE. The RE establishes widespread connections with several limbic structures. To correlate these projection patterns with the neurochemical characteristics of RE neurons, the retrograde tracer [3H]D-aspartate, which is selectively taken up by high affinity uptake sites that use glutamate as neurotransmitter, and the nonselective retrograde tracer wheatgerm agglutinin-conjugated colloidal gold was injected into the stratum lacunosum moleculare of the hippocampal CA1 subfield and into the medial septum. The results provide direct anatomical demonstration of aspartatergic/glutamatergic projection from the RE to the hippocampus and to the medial septum. Nearly all of the projecting neurons proved to be calbindin-immunopositive and many of them expressed calretinin. Both retrograde labelling techniques revealed that neurons projecting to the hippocampus were located in clusters in the dorsolateral part of the RE, whereas neurons projecting to the medial septum were mainly distributed in the ventromedial portion of the nucleus, indicating that different cell populations project to these limbic areas. These results suggest that neurons in the RE are heterogeneous and contribute to the excitatory innervation of the septo-hippocampal system.

Projections of the medial orbital and ventral orbital cortex in the rat

“…Finally, consistent with the present demonstration that MO primarily projects to the medial (MDm) and VO to lateral (MDl) divisions of MD, MDm, and MDl are the main sources of return projections to MO and VO, respectively (Ray and Price, 1992;Reep et al, 1996). Similar to MD, the nucleus reuniens (RE) is strongly reciprocally linked with the PFC-as well as with the hippocampus (Herkenham, 1978;Conde et al, 1990;Wouterlood et al, 1990;Wouterlood, 1991;Dolleman-Van der Weel and Witter, 1996;Risold et al, 1997;Bokor et al, 2002;Van der Werf et al, 2002;Vertes, 2002Vertes, , 2004Vertes, , 2006Jasmin et al, 2004;McKenna and Vertes, 2004;Vertes et al, 2006Vertes et al, , 2007Hoover and Vertes, 2007). Unlike the fairly extensive examination of the output of RE (Vertes, 2006;Vertes et al, 2006), few studies have described afferents to RE.…”

Afferent projections to nucleus reuniens of the thalamus

“…The nucleus reuniens is the major source of thalamic afferents to the hippocampus/parahippocampus and orbitomedial cortex (Herkenham, 1978;Ohtake and Yamada, 1989;Wouterlood et al, 1990;Wouterlood, 1991;Conde et al, 1995;Reep et al, 1996;Reep and Corwin, 1999;Bokor et al, 2002;Vertes et al, 2003). The present findings of widespread projections to RE, mainly from limbic/ limbic-associated structures, suggest that RE is involved in the transfer of limbic information (emotional/cognitive) to the hippocampus and prefrontal cortex.…”

“…We confirmed the massive mPFC input to RE and further demonstrated pronounced projections to RE from several sites of the cortex, hippocampus (subiculum), basal forebrain, amygdala, hypothalamus, and brainstem. These findings of strong and widespread afferents to RE suggest that RE may be critically involved in the integration and subsequent transfer of mulitmodal information from widespread sources to main RE targets, namely, the hippocampus and the orbital/medial prefrontal cortex (Herkenham, 1978;Ohtake and Yamada, 1989;Wouterlood et al, 1990;Wouterlood, 1991;Conde et al, 1995;Reep et al, 1996;Reep and Corwin, 1999;Bokor et al, 2002;Van der Werf et al, 2002;Vertes et al, 2002Vertes et al, , 2003Viana Di Prisco and Vertes, 2003).…”

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat

“…Field CA1 is, however, also targeted by an excitatory subcortical input that arises from the ventral thalamic midline nucleus reuniens (RE), of which the terminal distribution of axons in LM overlaps with the terminations of the direct EC-CA1 projection (Herkenham 1978;Wouterlood et al 1990;Dolleman-van der Weel et al 1994;Vertes et al 2006). In the rat, both RE and EC inputs affect the level of hippocampal excitability by targeting pyramidal cells as well as several types of local interneurons with a dendritic tree in LM (Wouterlood et al 1990;Colbert and Levy 1992;Desmond et al 1994;Empson and Heinemann 1995;Levy et al 1995;Dolleman-van der Weel et al 1997;Dolleman-van der Weel and Witter 2000;Bokor et al 2002;Klausberger 2009). Surprisingly, the overlap of RE and EC projections in CA1 and its relevance for hippocampal functioning has received little attention.…”