Adult hypothalamic neurogenesis has been recently reported, but the cell of origin and function of these newborn neurons are unknown. We utilize genetic fate mapping to show that median eminence tanycytes generate newborn neurons; blocking this neurogenesis alters weight and metabolic activity in adult mice. These findings describe a previously unreported neurogenic niche within the mammalian hypothalamus with important implications for metabolism.

Fear learning is associated with changes in synapse strength in the lateral amygdala (LA). To examine changes in LA dendritic spine structure with learning, we used serial electron microscopy to reconstruct dendrites after either fear or safety conditioning. The spine apparatus, a smooth endoplasmic reticulum (sER) specialization found in very large spines, appeared more frequently after fear conditioning. Fear conditioning was associated with larger synapses on spines that did not contain a spine apparatus, whereas safety conditioning resulted in smaller synapses on these spines. Synapses on spines with a spine apparatus were smaller after safety conditioning but unchanged with fear conditioning, suggesting a ceiling effect. There were more polyribosomes and multivesicular bodies throughout the dendrites from fear conditioned rats, indicating increases in both protein synthesis and degradation. Polyribosomes were associated with the spine apparatus under both training conditions. We conclude that LA synapse size changes bidirectionally with learning and that the spine apparatus has a central role in regulating synapse size and local translation. T he lateral amygdala (LA) fear circuit provides a unique model for investigating the synaptic basis of memory. The LA is critical for the acquisition and storage of auditory fear conditioning, a robust behavioral paradigm in which animals learn to associate a previously neutral tone with an aversive stimulus, such as a footshock (1, 2). In conditioned inhibition, tones and shocks are arranged such that the tone predicts the absence of the shock; the tone thus becomes associated with safety and suppresses fear (3). Tone-evoked physiological responses in the LA are strengthened with fear conditioning and weakened with conditioned inhibition, suggesting that LA synapse strength encodes the fear response to the tone (1, 2, 4-6).Auditory inputs to LA cells form synapses on dendritic spines, tiny compartments that may allow local regulation of synaptic transmission and structure (7-12). Experimentally-induced changes in synaptic strength such as long-term potentiation (LTP) and depression (LTD) alter spine size in immature hippocampus in vitro, with LTP generally associated with larger spines and LTD with smaller spines (13-16). Although LTP and LTD are considered models of learning, it is unknown whether spine structure is affected by associative learning in the adult animal. To address this question, we took advantage of the known effects of fear learning on LA synaptic strength and used serial section transmission electron microscopy (ssTEM) to reconstruct spiny dendrites from adult rat LA after either fear conditioning or conditioned inhibition training.Enlarged spines have been proposed as a locus for information storage, with smaller spines representing memory capacity (10,17). Very large spines typically contain a spine apparatus, a membranous organelle that has been reported to be involved in learning and synaptic plasticity (18). We found that the effects of learnin...

Optic nerve head (ONH) astrocytes have been proposed to play both protective and deleterious roles in glaucoma. We now show that, within the postlaminar ONH myelination transition zone (MTZ), there are astrocytes that normally express Mac-2 (also known as Lgals3 or galectin-3), a gene typically expressed only in phagocytic cells. Surprisingly, even in healthy mice, MTZ and other ONH astrocytes constitutive internalize large axonal evulsions that contain whole organelles. In mouse glaucoma models, MTZ astrocytes further upregulate Mac-2 expression. During glaucomatous degeneration, there are dystrophic processes in the retina and optic nerve, including the MTZ, which contain protease resistant γ-synuclein. The increased Mac-2 expression by MTZ astrocytes during glaucoma likely depends on this γ-synuclein, as mice lacking γ-synuclein fail to up-regulate Mac-2 at the MTZ after elevation of intraocular pressure. These results suggest the possibility that a newly discovered normal degradative pathway for axons might contribute to glaucomatous neurodegeneration.DBA/2J mice | retinal ganglion cell | Sncg G laucoma, a neurodegenerative disorder that kills retinal ganglion cells (RGCs), affects more than 60 million people and is the second leading cause of blindness worldwide (1). In glaucomatous retinas, both astrocytes and Müller glia increase their reactivity (2, 3). Within the orbital portion of the optic nerve, astrocytes increase in number and reactivity (4). Within the optic nerve head (ONH), astrocytes also increase reactivity in glaucoma animal models and in the human disease (5). These ONH astrocytes are of particular interest as they enwrap axons at the location where damage would account for the arcuate vision field loss characteristic of glaucoma.Here, we identify a spatially discrete population of astrocytes within the ONH, those at the myelination transition zone (MTZ), which express the phagocytosis-related gene Mac-2. Surprisingly, astrocytes throughout the ONH including the MTZ phagocytose large axonal evulsions even in unaffected mice. Mac-2 expression is increased in optic nerve astrocytes upon injury and at the MTZ in two mouse models of glaucoma. In glaucomatous mice, there are protease resistant forms of γ-synuclein, including at the MTZ. Further, mice lacking γ-synuclein fail to up-regulate Mac-2 at the MTZ in response to increased intraocular pressure (IOP). These results suggest the possibility that failure to properly clear axon-derived material at the MTZ, including γ-synuclein, may contribute to axon loss in glaucoma.