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  4. Saporin lesions that target suprachiasmatic cells bearing NPY receptors eliminate or greatly impair circadian rhythm generation and entrainment.

Saporin lesions that target suprachiasmatic cells bearing NPY receptors eliminate or greatly impair circadian rhythm generation and entrainment.

Morin LP, Studholme KM (2009) Saporin lesions that target suprachiasmatic cells bearing NPY receptors eliminate or greatly impair circadian rhythm generation and entrainment. Neuroscience 2009 Abstracts 278.7/EE49. Society for Neuroscience, Chicago, IL.

Summary: General destruction of the SCN caused by electrical lesions produce loss of circadian rhythmicity and entrainment. More specific, cell-directed lesion methods, such as the use of NMDA as a neurotoxin, have not been successful. Here, we describe the use of the ribotoxin, Saporin (SAP), to kill specific types of SCN neurons and show the effects of such selective lesions on the hamster circadian locomotor rhythm. Adult male golden hamsters were injected bilaterally with 200 nL of a SAP/neuropeptide conjugate into the SCN bilaterally. The neuropeptides were neuropeptide Y (NPY), cholecystokinin (CCK) or substance P (SP). NPY terminals are distributed throughout the SCN; CCK and SP cells are present in the SCN and there have been NPY and SP receptors described in the hamster SCN. SAP/NPY (N=10) treatment caused arrhythmicity in 4 animals under LD conditions and 4 others became arrhythmic when transferred to DD. Arrhythmicity occurred in 1/9, 0/8 and 0/10 animals treated with SAP/CCK, SAP/SP or vehicle. There was also a significant effect of treatment on the level of variability of the activity records as indicated by precision of activity onset (p<.008) and approximate entropy analysis of disorder within the running record (p<.004). The SAP/NPY group accounted for nearly all the between-group variability. The histology showed a large decrease in the number of SCN cells, but there were many cells remaining after SAP/NPY treatment. Care was taken to determine that the remaining cells were, in fact, neurons. Also, the brains of lesioned animals retained reasonably intact RHT, GHT and 5HT input pathways. Normal histology evaluated for NeuN, a neuronal antigen, showed that an unexpected pattern of NeuN-IR cells in the SCN of normal animals, with the majority of such neurons found in an area that includes the SCNce and the region dorsolateral. NeuN was heavily co-localized with calbindin-IR in cells of the SCNce, but not with VP- or VIP-IR. This distribution of SCN cells containing NeuN-IR was approximately the same in both mice and hamsters. Conclusions: (1) SAP/NPY lesions many, but not all SCN neurons; (2) Such lesions result in massive degradation of circadian rhythmicity; (3) The three main SCN input pathways remain essentially intact after SAP treatment; (4) NeuN-IR neurons are distributed in a novel pattern in the SCN of both mouse and hamster; (5) Presently unidentified SCN cells bearing NPY receptors are likely to be critical to the generation of cohesive circadian rhythms, whereas those bearing SP or CCK receptors are minimally, if at all involved.

Related Products: CCK-SAP (Cat. #IT-31), SSP-SAP (Cat. #IT-11), NPY-SAP (Cat. #IT-28)