Immunohistochemical characterization of substance P receptor (NK(1)R)-expressing interneurons in the entorhinal cortex.
It has been reported that application of substance P (SP) to the medial portion of the entorhinal cortex (EC) induces a powerful antiepileptic effect (Maubach et al. [1998] Neuroscience 83:1047-1062). This effect is presumably mediated via inhibitory interneurons expressing the neurokinin-1 receptor (NK(1)R), but the existence of NK(1)R-expressing inhibitory interneurons in the EC has not yet been reported. The present immunohistochemical study was performed in the rat to examine the existence and distribution of NK(1)R-expressing neurons in the EC as well as any co-expression of other neurotransmitters/neuromodulators known to be associated with inhibitory interneurons: gamma-aminobutyric acid (GABA), parvalbumin (PARV), calretinin (CT), calbindin (CB), somatostatin (SST), and neuropeptide Y (NPY). Our results indicated that NK(1)R-positive neurons were distributed rather sparsely (especially in the medial EC), primarily in layers II, V, and VI. The results of our double-immunohistochemical staining indicated that the vast majority of NK(1)R-expressing neurons also expressed GABA, SST, and NPY. In addition, CT was co-expressed in a weakly stained subgroup of NK(1)R-expressing neurons, and CB was co-expressed very rarely in the lateral EC, but not in the medial EC. In contrast, SP-immunopositive axons with fine varicosities were distributed diffusely throughout all layers of the EC, appearing to radiate from the angular bundle. SP may be released in a paracrine manner to activate a group of NK(1)R-expressing entorhinal neurons that co-express GABA, SST, and NPY, exerting a profound inhibitory influence on synchronized network activity in the EC.
Wolansky
Trish
T
Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2R3.
Pagliardini
Silvia
S
Greer
John J
JJ
Dickson
Clayton T
CT
D000818:Animals; D003952:Diagnostic Imaging; D018728:Entorhinal Cortex / Q000166:cytology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018040:Receptors, Neurokinin-1; D013373:Substance P; D005680:gamma-Aminobutyric Acid