Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain

Abstract

Using antibodies to neuropeptide Y (NPY) in combination with immunohistochemical techniques we have studied the distribution of cell bodies and nerve terminals containing NPY immunoreactivity (-i) in the hippocampal region of rats and monkeys (cynomolgus). In colchicine-pretreated rats a large number of NPY-positive cells are present in all areas of the hippocampal region. The NPY-i cells range in size from small (diameter across soma: 10-15 micron) to large (approximately 20 micron). Most of the NPY-i cells are situated in the hilus, in the subgranular zone of the area dentata, and in the stratum oriens of Ammon's horn. A majority of these are polymorphic cells but cells of different morphology are present in these layers as well. These include small spheroid cells and dentate pyramidal basket cells that are distinct from the polymorphic cells in the subgranular zone. The subicular complex (e.g., the subiculum, pre-, and parasubiculum) and the entorhinal area contain fewer NPY-i cells than the rest of the hippocampal region. In the dorsal parts of the pre- and parasubiculum numerous small cells are scattered throughout all layers, while in the entorhinal area the NPY-stained cells are situated primarily in the deep layers (V and VI). In the ventral part of the lateral entorhinal area large multipolar and bitufted cells are found in layers II-VI. In the untreated monkey brain NPY-positive cells are found in the hilus of the area dentata and in the deep (IV through VI) layers of both the medial and lateral entorhinal area. Fewer NPY-stained cells are present in the subicular complex and in the entorhinal area. In the monkey as well as in the rat, NPY-stained cells are present in the angular bundle and in the alveus. A dense network of NPY-i fibers innervates the entire hippocampal region in both the rat and the monkey. The hippocampal NPY-i preterminal processes are present primarily in stratum moleculare of Ammon's horn and in the outer one-third of this layer in the area dentata. The NPY-positive innervation of the dentate molecular layer is far more prominent in the monkey than in the rat brain. Numerous NPY-stained fibers are scattered in other areas as well. In all retrohippocampal structures, and in particular the entorhinal area, the NPY-i fibers form a massive network that innervates all layers to about the same extent, with the exception of the molecular layer, which is more densely innervated than the other layers.

Neuropeptide Y and Epilepsy

“…Similarly, in the in vitro models of ictal activity such as the stimulus train-induced bursting (STIB; 30) and related models (31), the primary afterdischarge mimics the tonicclonic characteristics of limbic seizures and responds to clinically effective concentrations of anticonvulsants (AEDs) that are effective on complex partial seizures (32). NPY, peptide YY (PYY), and the Y 2 receptor-selective agonist, [ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY, potently inhibited the afterdischarge (29; see later for details about NPY receptors), whereas the Y 1 and Y 5 receptor-preferring ligand, Leu 31 , Pro 34 NPY was without effect on the afterdischarge in this model (29,33), suggesting the importance of the Y 2 receptor in NPY action (see later). Finally, NPY has been tested in slices of the frontal neocortex against seizure activity induced by a 0-Mg 2 ϩ solution.…”

“…Our laboratory recently tested this question by using a newly developed antagonist to the Y 2 receptor, BIIE 0246 (50), which profoundly reduced the presynaptic response to NPY and to the selective Y 2 -receptor agonist, [ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY (51). Indeed, 30 n M BIIE 0246 reduced the effect of NPY in area CA1 of hippocampal slices to 40% of control levels (52; Fig.…”

The Effect of Intrahippocampal Injection of Group II and III Metobotropic Glutamate Receptor Agonists on Anxiety; the Role of Neuropeptide Y

“…It contains numerous NPY interneurons and is rich in mGluRs (Kohler et al, 1986;Redrobe et al, 1999;Dumont et al, 1998). It was revealed that the enhancement of glutamatergic transmission strongly stimulated NPY synthesis and/or increased the content of that peptide in the hippocampus Bellmann et al, 1991;Schwarzer et al, 1996).…”

Plasticity of neuropeptide Y in the dentate gyrus after seizures, and its relevance to seizure-induced neurogenesis

“…NPY is normally expressed very specifically in GABAergic neurons and not other cell types [6,7]. Fiber systems that innervate the dentate gyrus do not appear to express NPY.…”

“…However, there are some general rules that can be concluded. First, most of the cell bodies are located in the hilus and in the granule cell layer [7]. In addition, these neurons appear mostly to be "local circuit neurons" because their axon typically arborizes in the hippocampal lamella where the cell body is located.…”