title: Septal projections to nucleus incertus in the rat: bidirectional pathways for modulation of hippocampal function.
abstract: Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)-67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.
authors.affiliation: Departamento de Medicina, Universitat Jaume I, 12071, Castellón, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sánchez-Pérez
authors.forename: Isabel
authors.initials: I
authors.lastname: Arnal-Vicente
authors.forename: Fabio N
authors.initials: FN
authors.lastname: Santos
authors.forename: Celia W
authors.initials: CW
authors.lastname: Pereira
authors.forename: Nisrin
authors.initials: N
authors.lastname: ElMlili
authors.forename: Julio
authors.initials: J
authors.lastname: Sanjuan
authors.forename: Sherie
authors.initials: S
authors.lastname: Ma
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gundlach
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Olucha-Bordonau
mesh_terms: D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology* / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D011149:Pons / Q000033:anatomy & histology* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000033:anatomy & histology* / Q000378:metabolism; D013266:Stilbamidines
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; C576512:Calb2 protein, rat; D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins; D013266:Stilbamidines; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: GABA; anxiety; arousal; calretinin; nucleus incertus; septohippocampal system; spatial and emotional learning; theta rhythm