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In the published article, the author name Leila Toulabi was missed during the proof stage and it has been now updated. Section on Cellular Neurobiology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, 49, Convent Drive, Bldg 49, Rm 6A‑10, Bethesda, MD 20892, USA. The original article has been updated.

An in-depth understanding of the anatomy discipline is essential for the work of healthcare professionals. In recent decades, the content and time of teaching anatomy have decreased in all health science degrees. The aim of this study was to look for alternatives for compensating the reduction of the teaching of anatomy by supplementing students with a practical training course and to know evaluations of the course given by students enrolled in the degree in Speech Therapy and its impact on their academic results. All students (100%) positively evaluated having acquired skills and attitudes for their future professional life. The majority of the students (95.8%) believed that their knowledge was acceptable; 97.2% of the students thought they would have the possibility to apply their acquired anatomical knowledge as professionals; 98.5% were satisfied with the voluntary course; and finally, the percentage of students that passed the "Anatomophysiology of language and voice organs" course increased from previous academic years. Optional (theoretical/practical) undergraduate courses can be used in parallel to overcome the devaluation of anatomical studies in new curricula. The optional undergraduate anatomy course in the Speech Therapy program has been positively evaluated because it stimulated students' motivation and appealed to their interest in anatomy. Students considered that these courses would help them in their training and they could put what they had learned into practice in their future professions. However, very little evidence for the impact of optional practical courses exists, yet it could be an efficient method to increase anatomical knowledge.

Protecting neurons from death during oxidative and neuroexcitotoxic stress is key for preventing cognitive dysfunction. We uncovered a novel neuroprotective mechanism involving interaction between neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor with no previously known neurological function. Co-immunoprecipitation and pull-down assays confirmed interaction between NFα1/CPE and 5-HTR1E and 125I NF-α1/CPE-binding studies demonstrated saturable, high-affinity binding to 5-HTR1E in stably transfected HEK293 cells (Kd = 13.82 nM). Treatment of 5-HTR1E stable cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented a decrease in pro-survival protein, BCL2, during H2O2-induced oxidative stress. Cell survival assay in β-arrestin Knockout HEK293 cells showed that the NF-α1/CPE-5-HTR1E-mediated protection against oxidative stress was β-arrestin-dependent. Molecular dynamics studies revealed that NF-α1/CPE interacts with 5-HTR1E via 3 salt bridges, stabilized by several hydrogen bonds, independent of the serotonin pocket. Furthermore, after phosphorylating the C-terminal tail and intracellular loop 3 (ICL3) of NF-α1/CPE-5-HTR1E, it recruited β-arrestin1 by forming numerous salt bridges and hydrogen bonds to ICL2 and ICL3, leading to activation of β-arrestin1. Immunofluorescence studies showed 5-HTR1E and NF-α1/CPE are highly expressed and co-localized on cell surface of human hippocampal neurons. Importantly, knock-down of 5-HTR1E in human primary neurons diminished the NF-α1/CPE-mediated protection of these neurons against oxidative stress and glutamate neurotoxicity-induced cell death. Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB/BCL2 pathway to mediate stress-induced neuroprotection. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-04021-3.

Introduction: The entorhinal cortex is among the earliest areas involved in Alzheimer’s disease. Volume reduction and neural loss in this area have been widely reported. Human entorhinal cortex atrophy is, in part, due to neural loss, but microglial and/or astroglial involvement in the different layers remains unclear. Additionally, -omic approaches in the human entorhinal cortex are scarce. Methods: Herein, stereological layer-specific and proteomic analyses were carried out in the human brain. Results: Neurodegeneration, microglial reduction, and astrogliosis have been demonstrated, and proteomic data have revealed relationships with up- (S100A6, PPP1R1B, BAG3, and PRDX6) and downregulated (GSK3B, SYN1, DLG4, and RAB3A) proteins. Namely, clusters of these proteins were related to synaptic, neuroinflammatory, and oxidative stress processes. Discussion: Differential layer involvement among neural and glial populations determined by proteinopathies and identified proteins related to neurodegeneration and astrogliosis could explain how the cortical circuitry facilitates pathological spreading within the medial temporal lobe., Introducción La corteza entorrinal se encuentra entre las primeras áreas involucradas en la enfermedad de Alzheimer. La reducción de volumen y la pérdida neural en esta área han sido ampliamente reportadas. La atrofia de la corteza entorrinal humana se debe, en parte, a la pérdida neural, pero la participación microglial y/o astroglial en las diferentes capas sigue sin estar clara. Además, los enfoques -ómicos en la corteza entorrinal humana son escasos. Métodos En este documento, se llevaron a cabo análisis proteómicos y específicos de capa estereológica en el cerebro humano. Resultados Se ha demostrado la neurodegeneración, la reducción microglial y la astrogliosis, y los datos proteómicos han revelado relaciones con proteínas reguladas al alza (S100A6, PPP1R1B, BAG3 y PRDX6) y a la baja (GSK3B, SYN1, DLG4 y RAB3A). Es decir, los grupos de estas proteínas estaban relacionados con procesos de estrés oxidativo, neuroinflamatorio y sináptico. Discusión La participación de capas diferenciales entre poblaciones neurales y gliales determinada por proteinopatías y proteínas identificadas relacionadas con la neurodegeneración y la astrogliosis podría explicar cómo el circuito cortical facilita la propagación patológica dentro del lóbulo temporal medial.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly. Progressive accumulation of insoluble isoforms of amyloid-β peptide (Aβ) and tau protein are the major neuropathologic hallmarks, and the loss of cholinergic pathways underlies cognitive deficits in patients. Recently, glial involvement has gained interest regarding its effect on preservation and impairment of brain integrity. The limbic system, including temporal lobe regions and the olfactory bulb, is particularly affected in the early stages. In the early 1980s, the reduced expression of the somatostatin neuropeptide was described in AD. However, over the last three decades, research on somatostatin in Alzheimer’s disease has been scarce in humans. Therefore, the aim of this study was to stereologically quantify the expression of somatostatin in the human hippocampus and olfactory bulb and analyze its spatial distribution with respect to that of Aβ and au neuropathologic proteins and astroglia. The results indicate that somatostatin-expressing cells are reduced by 50% in the hippocampus but are preserved in the olfactory bulb. Interestingly, the coexpression of somatostatin with the Aβ peptide is very common but not with the tau protein. Finally, the coexpression of somatostatin with astrocytes is rare, although their spatial distribution is very similar. Altogether, we can conclude that somatostatin expression is highly reduced in the human hippocampus, but not the olfactory bulb, and may play a role in Alzheimer’s disease pathogenesis.

Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disease that is pathologically described as a six-stage α-synucleinopathy. In stage 4, α-synuclein reaches the hippocampus, inducing cognitive deficits, from which it progresses to the isocortex, leading to dementia. Among hippocampal fields, cornu ammonis 2 is particularly affected by this α-synucleinopathy and critical for cognitive decline. Volumetric studies using magnetic resonance imaging have produced controversial results, with only some reporting volume loss, whereas stereological data obtained using nonspecific markers do not reveal volume changes, neural or glial loss. Proteomic analysis has not been carried out in the hippocampus of patients with PD. Objective: This study aims to explain hippocampal changes in patients with PD at the cellular and proteomic levels. Methods: α-Synuclein inclusions, volume and neural (NeuN), microglial (Iba-1) and astroglial (GFAP) populations were stereologically analyzed. SWATH-MS quantitative proteomic analysis was also conducted. Results: Area fraction fractionator probe revealed a higher area fraction α-synucleinopathy in cornu ammonis 2. No volume change, neurodegeneration, microgliosis or astrogliosis was detected. Proteomic analysis identified 1,634 proteins, of which 83 were particularly useful for defining differences among PD and non-PD groups. Among them, upregulated (PHYIP, CTND2, AHSA1 and SNTA1) and downregulated (TM163, REEP2 and CSKI1) proteins were related to synaptic structures in the diseased hippocampus. Conclusion: The distribution of α-synuclein in the hippocampus is not associated with volumetric, neural or glial changes. Proteomic analysis, however, reveals a series of changes in proteins associated with synaptic structures, suggesting that hippocampal changes occur at the synapse level during PD.

Dissections are a fundamental practical methodology for teaching human anatomy. However, this experience can be stressful, generating anxiety situations among students. This study tries to understand the attitudes, reactions, fears and anxiety state among students earning a physiotherapy degree when facing their first prosection. A cross-sectional before-and-after study was carried out with students who were provided with an anonymous "ad hoc" questionnaire and the State-Trait Anxiety Inventory (STAI).The values obtained from the total STAI questionnaire remained stable and unchanged during the prosection (p0.05). The levels of trait anxiety (TA) and state anxiety (SA) remained stable except in female students, who showed higher TA and SA scores, with a significance of p0.05 before and after the prosection. Although 100% of the students were satisfied with the dissection practices, the experience can provoke stressful responses and should be addressed using coping mechanisms, especially among female students.

Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease, and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus) of network dysfunction in Alzheimer’s and Parkinson’s diseases.

Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders in aging. Hyposmia has been described as an early symptom that can precede cognitive and motor deficits by decades. Certain regions within the olfactory system, such as the anterior olfactory nucleus, display the neuropathological markers tau and amyloid-β or α-synuclein from the earliest stages of disease progression in a preferential manner. Specific neuronal subpopulations, namely those expressing somatostatin (SST), are preferentially affected throughout the olfactory and limbic systems. SST is a neuropeptide present in a subpopulation of GABAergic interneurons throughout the brain and its main function is to inhibit principal neurons and/or other interneurons. It has been reported that SST expression is reduced by 50% in Alzheimer's disease and that it is related to the formation of Aβ oligomers. The mechanisms underlying the preferential vulnerability of SST-expressing neurons in Alzheimer's disease (and, to a minor extent, in Parkinson's disease) are not known but analysis of the available data could shed light on their etiology. This short review aims to update the knowledge of functional features of somatostatin within the olfactory system and its role in olfactory deficits during neurodegeneration.

Practical training in the dissection of human cadavers is a fundamental and traditional component of human anatomy education in medical schools. This practice, however, can be stressful for students and can generate a certain amount of anxiety. The aim of this study is to explore the attitudes, reactions, and anxiety levels of first-year medical students when working in the dissecting room, over a period of one year, and to relate these anxiety levels to the results of our educational program. This is a before and after descriptive study of students at the University of Castilla-La-Mancha. Questionnaires were distributed among them before and after their dissection practices in order to understand their feelings and emotions and their satisfaction about this activity. State-Trait Anxiety Inventory questionnaires were used to assess the students' 'state anxiety' (SA), which dropped significantly from 49.1% to 14% by the end of their first year. Female students started with higher levels of SA than their male counterparts but by the end of the year these had dropped to similar levels. Anxiety and fearful thoughts tended to drop (P > 0.05). In contrast, uncertainty levels showed significant changes, falling from 44.4% to 12.3%. Nonetheless, 100% of students would go through the experience again. Indeed, 98.2% considered that dissection practices were useful in reinforcing the theoretical aspects of their education, and 80.7% believed that dissecting was more useful than theoretical models. Although students were satisfied with dissection practices the experience cause stressful responses.

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 302:394-404, 2019. © 2018 Wiley Periodicals, Inc.

Human anatomy education often utilizes the essential practices of cadaver dissection and examination of prosected specimens. However, these exposures to human cadavers and confronting death can be stressful and anxiety-inducing for students. This study aims to understand the attitudes, reactions, fears, and states of anxiety that speech therapy students experience in the dissection room. To that end, a before-and-after cross-sectional analysis was conducted with speech therapy students undertaking a dissection course for the first time. An anonymous questionnaire was administered before and after the exercise to understand students' feelings and emotions. State-Trait Anxiety Inventory questionnaires (STAI-S and STAI-T) were used to evaluate anxiety levels. The results of the study revealed that baseline anxiety levels measured using the STAI-T remained stable and unchanged during the dissection room experience (P > 0.05). Levels of emotional anxiety measured using the STAI-S decreased, from 15.3 to 11.1 points (P 0.05). A total of 63.4% of students described having thoughts about life and death. After the session, 100% of students recommended the dissection exercise, giving it a mean score of 9.1/10 points. Anatomy is an important subject for students in the health sciences, and dissection and prosection exercises frequently involve a series of uncomfortable and stressful experiences. Experiences in the dissection room may challenge some students' emotional equilibria. However, students consider the exercise to be very useful in their education and recommend it. Anat Sci Educ 10: 487-494. © 2017 American Association of Anatomists.

Dissection and prosection practices using human cadavers are a key component of macroscopic anatomy education in different Health Sciences university degrees. However, first-hand interaction with cadavers can be distressing for students, generating anxiety on a number of levels. This study aims to shed light on the reactions, fears and different states of anxiety experienced by nursing students in to a single anatomy room experience over a five-hour period, and examined reactions pre and post same. A descriptive study of these students was designed in order to understand their feelings and emotions, based on the distribution of anonymous "ad hoc" questionnaires before and after the practices. Also, State-Trait Anxiety Inventory (STAI) questionnaires were administered in order to assess their anxiety levels: Trait Anxiety (TA), which measures basal anxiety levels, and State Anxiety (SA), which measures individual emotional responses during a specific event (in this case, the prosection practice). The results of this study indicate that basal anxiety levels, measured as TA, remained stable and unchanged during the practice (p 0.05). SA or emotional anxiety levels, on the other hand, dropped from 21.3 to 17.8 points (p 0.05). Before the start of the practical exercise, 17.6% of the students admitted experiencing some kind of anxiety. Afterwards, however, 90.2% of the students said they would recommend these practices. They considered that prosection practices very useful for their education and recommended that they be retained for future courses. However, our study also showed the relevance of using coping mechanisms before the first contact with the dissecting room, especially for those students who did not feel emotionally prepared for it beforehand.

[Background]: Intracerebral inoculation of extracts from post-mortem human Alzheimer’s disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cytosolic protein aggregates, suggest that brain extracts contain key contributors that enhance the prion-like effect of amyloid-β. Nevertheless, these potential partners are still unknown due to the complexity of whole brain extracts., [Methods]: Herein, we established a method based on sequential detergent solubilization of post-mortem samples of human brains affected by Alzheimer’s disease that strongly enrich amyloid-β aggregates by eliminating 92% of the remaining proteins. Internalization of Aβ1–42 from the enriched AD extracts was evaluated in vitro, and internalization of fluorescent-labeled AD extracts was also investigated in vivo. Furthermore, we carried out a molecular characterization of the Aβ-enriched fraction using label-free proteomics, studying the distribution of representative components in the amygdala and the olfactory cortex of additional human AD brain samples by immunohistochemistry., [Results]: Aβ1–42 from the enriched AD extracts are internalized into endothelial cells in vitro after 48 h. Furthermore, accumulation of fluorescent-labeled Aβ-enriched extracts into mouse microglia was observed in vivo after 4 months of intracerebral inoculation. Label-free proteomics (FDR < 0.01) characterization of the amyloid-β-enriched fraction from different post-mortem samples allowed for the identification of more than 130 proteins, several of which were significantly overrepresented (i.e., ANXA5 and HIST1H2BK; p < 0.05) and underrepresented (i.e., COL6A or FN1; p < 0.05) in the samples with Alzheimer’s disease. We were also able to identify proteins exclusively observed in Alzheimer’s disease (i.e., RNF213) or only detected in samples not affected by the disease (i.e., CNTN1) after the enrichment process. Immunohistochemistry against these proteins in additional tissues revealed their particular distribution in the amygdala and the olfactory cortex in relation to the amyloid-β plaque., [Conclusions]: Identification and characterization of the unique features of these extracts, in terms of amyloid-β enrichment, identification of the components, in vitro and in vivo cell internalization, and tissue distribution, constitute the best initial tool to further investigate the seeding and transmissibility proposed in the prion-like hypothesis of Alzheimer’s disease., Sponsored by the Spanish Ministry of Economy and Competitiveness-FEDER (grant # SAF2016-75768-R) to AMM, MINECO-RETOS (AEI-FEDER) to MDP, and the Autonomous Government of Castilla-La Mancha/FEDER (grant no. SBPLY/ 17/180501/000430) to AMM and DSS.

Parkinson’s disease (PD) is a synucleinopathy that has multiple neuropathological characteristics, with nigrostriatal dopamine system degeneration being a core feature. Current models of PD pathology typically fail to recapitulate several attributes of the pathogenic process and neuropathology. We aimed to define the effects of combining a mouse model exhibiting multiple PD-like changes with intrastriatal injections of α-synuclein (α-syn) pre-formed fibril (PFFs) aggregates. We employed the heterozygous Engrailed 1 (En1+/–) mouse that features several pathophysiological hallmarks of clinical PD., La enfermedad de Parkinson (EP) es una sinucleinopatía que tiene múltiples características neuropatológicas, siendo la degeneración del sistema dopaminérgico nigroestriatal una característica central. Los modelos actuales de patología de la EP generalmente no logran recapitular varios atributos del proceso patogénico y la neuropatología. Nuestro objetivo fue definir los efectos de combinar un modelo de ratón que presentaba múltiples cambios similares a los de la EP con inyecciones intraestriatales de agregados de fibrillas preformadas (PFF) de α-sinucleína (α-syn). Empleamos el ratón heterocigoto Engrailed 1 (En1+/–) que presenta varias características fisiopatológicas de la EP clínica.

Background Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients. Methods The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed. Results In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus. Conclusions The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society

Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease’s progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON. First, we determined the expression of the calcium binding interneuron markers, calretinin, calbindin and parvalbumin, as well as non-calcium binding interneuron marker, somatostatin, in neuronal cell bodies alone (cells/mm2) and in neuronal cell bodies and neurites (% of area fraction) of post-mortem tissue from PD cases and age-matched controls (n = 4 for each) by immunofluorescent confocal microscopy. Results indicated that parvalbumin expression was upregulated in neuronal cell bodies throughout the anterior olfactory nucleus of PD cases compared with controls. Furthermore, there was increased calbindin, calretinin and parvalbumin expression in the cell bodies and neurites of neurons in the retrobulbar division and also increased parvalbumin expression in the neurites of neurons in the cortical division; calretinin expression was also increased in neuronal cell bodies and neurites in the cortical posterior division. Second, we analyzed the co-localization of the above markers with α-synuclein, with results indicating that α-synuclein co-localized with the calcium-binding proteins, but only partially with somatostatin. Taken together, these results indicate differential expression levels among different neural markers in the divisions of the AON in PD cases and point to several possibilities, among them: possible neuroprotective mechanisms of calcium-binding proteins against α-synuclein; and the differential involvement of somatostatin in α-synuclein-positive cell bodies and neurites.

Human anatomy education often utilizes the essential practices of cadaver dissection and examination of prosected specimens. However, these exposures to human cadavers and confronting death can be stressful and anxiety-inducing for students. This study aims to understand the attitudes, reactions, fears, and states of anxiety that speech therapy students experience in the dissection room. To that end, a before-and-after cross-sectional analysis was conducted with speech therapy students undertaking a dissection course for the first time. An anonymous questionnaire was administered before and after the exercise to understand students' feelings and emotions. State-Trait Anxiety Inventory questionnaires (STAI-S and STAI-T) were used to evaluate anxiety levels. The results of the study revealed that baseline anxiety levels measured using the STAI-T remained stable and unchanged during the dissection room experience (P 0.05). Levels of emotional anxiety measured using the STAI-S decreased, from 15.3 to 11.1 points (P 0.05). In the initial phase of the study, before any contact with the dissection room environment, 17% of students experienced anxiety, and this rate remained unchanged by end of the session (P 0.05). A total of 63.4% of students described having thoughts about life and death. After the session, 100% of students recommended the dissection exercise, giving it a mean score of 9.1/10 points. Anatomy is an important subject for students in the health sciences, and dissection and prosection exercises frequently involve a series of uncomfortable and stressful experiences. Experiences in the dissection room may challenge some students' emotional equilibria. However, students consider the exercise to be very useful in their education and recommend it. Anat Sci Educ 10: 487-494. © 2017 American Association of Anatomists.

Alzheimer´s disease is the most prevalent neurodegenerative disease, mostly idiopathic and with palliative treatment. Neuropathologically, it is characterized by intracellular neurofibrillary tangles of tau protein and extracellular plaques of amyloid β peptides. The relationship between Alzheimer’s disease and neurogenesis is unknown, but two facts are particularly relevant. First, early aggregation sites of both proteinopathies include the hippocampal formation and the olfactory bulb, which have been correlated to memory and olfactory deficits, respectively. These areas are well-recognized integration zones of newly-born neurons in the adult brain. Second, molecules, such as amyloid precursor protein and presenilin-1 are common to both Alzheimer’s disease etiology and neurogenic development. Adult neurogenesis in Alzheimer’s disease models has been studied in the hippocampus, but only occasionally addressed in the olfactory bulb and results are contradictory. To gain insight on the relationship between adult neurogenesis and Alzheimer’s disease, this work analyzes neurogenesis, neurodegeneration, interneuron vulnerability and amyloid-β involvement in the olfactory bulb of an Alzheimer’s disease model. Control and double-transgenic mice carrying the amyloid precursor protein and the presenilin-1 genes, which give rise amyloid β plaques have been used. BrdU-treated animals have been studied at 16, 30, 43 and 56 weeks of age. New-born cell survival (BrdU), neuronal loss (using neuronal markers NeuN and PGP9.5), differential interneuron (calbindin-, parvalbumin-, calretinin- and somatostatin-expressing populations) vulnerability and involvement by amyloid β have been analyzed. Neurogenesis increases with aging in the granule cell layer of control animals from 16 to 43 weeks. No neuronal loss has been observed after quantifying NeuN or PGP9.5. Regarding interneuron population vulnerability: calbindin-expressing neurons remains unchanged; parvalbumin-expressing neurons trend to increase with aging in transgenic animals; calretinin-expressing neurons increase with aging in transgenic mice and decrease in control animals and neurogenesis is higher in control as compared to transgenic animals at given ages, finally; somatostatin-expressing neurons of transgenic mice decrease with aging and as compared to controls. Amyloid β aggregates with aging in the granule cell layer, which may be related to the particular involvement of somatostatin-expressing cells.

Olfactory deficits are an early feature of Parkinson's disease (PD). Neuropathologically, α-synucleinopathy (Lewy bodies and neurites) is observed earlier (stage 1) in the olfactory system than in the substantia nigra (stage 3), and this could underlies the early olfactory symptoms. In the present report, we analyzed the distribution of α-synuclein deposits in tertiary olfactory structures (anterior olfactory nucleus, olfactory tubercle, piriform cortex, posterolateral cortical amygdala and lateral entorhinal cortex) of homozygous transgenic mice (aged 2-8 months) overexpressing the human A53T variant of α-synuclein. To address the hypothesis of progressive α-synucleinopathy within the olfactory system, the distribution of α-synuclein was analyzed in conjunction with tracer injections into the main olfactory bulb. The time-course of α-synuclein expression revealed a significant increase in the piriform cortex at the age of 8 months compared to other brain structures. Tracing experiments revealed that olfactory projections are reduced in homozygous as compared to wild type animals. Double-labeling experiments show labeled axonal collaterals of mitral cells entering layer II of the piriform cortex in close proximity to α-synuclein-positive cells. To our knowledge, this is the first study addressing the progression of α-synuclein expression in a vulnerable neuronal pathway in PD.

The olfactory and vomeronasal epithelia detect chemical stimuli in most tetrapods. Both epithelia undergo neural replacement during adulthood. In the central regions of vomeronasal epithelium, similar rates of neurogenesis and apoptosis evidence balanced replacement mechanisms. In the margins, the rate of neurogenesis is several times higher as compared with the rate of apoptosis suggesting net addition of neural receptor cells during adulthood. Herein, the fate of these marginal neuroblasts has been investigated in adult mice. Newly born and mature receptor neurons have been labeled. In the margins, more than 60% of new-born cells send axons to the accessory olfactory bulb. These results evidence that new neural elements from the vomeronasal epithelium are added to the accessory olfactory bulb preexisting circuitry.

The vomeronasal sensory epithelium contains two distinct populations of vomeronasal sensory neurons. Apical neurons express Gi2α-linked V1R vomeronasal receptors and project to the anterior portion of the accessory olfactory bulb, while basal neurons express Goα-linked V2R receptors and project to the posterior portion. Sensory neurons expressing V1R and V2R vomeronasal receptors are sensitive to different stimuli. Neurons in the vomeronasal system undergo continuous cell turnover during adulthood. To analyze over time neurogenesis of the different sensory cell populations, adult mice were injected with bromodeoxyuridine (BrdU) and sacrificed at postinjection days 1, 3, 5, 7, and 11. Newborn vomeronasal neurons were revealed by antibodies against BrdU while subclasses of vomeronasal neurons were identified using antibodies against Goα or Gi2α proteins. To ascertain whether G proteins are early expressed during neurogenesis, multiple labeling experiments using PSA-NCAM and doublecortin were performed. Distribution of BrdU-labeled cells was analyzed in angular segments from the margin of the sensory epithelium. No sexual differences were found. Within survival groups, BrdU-Goα labeled cells were found more marginally when compared with BrdU-Gi2α labeled cells. The number of BrdU-positive cells decreased from day 1 to day 3 to remain constant afterwards. The relative proportions of BrdU-Gi2α and BrdU-Goα labeled cells remained similar and constant from postinjection day 1 onwards. This rate was also comparable with BrdU-positive cells starting day 3. These results indicate an early, constant, and similar rate of neurogenesis in the two major subclasses of vomeronasal neurons, which suggests that both cell populations maturate independently. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 961–970, 2010

Impaired olfaction is an early symptom of Alzheimer disease (AD). This likely to reflect neurodegenerative processes taking place in basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus. Betaeta-amyloid (Abeta) accumulation in AD brain may relate to decline in somatostatin levels: somatostatin induces the expression of the Abeta-degrading enzyme neprilysin and somatostatin deficiency in AD may therefore reduce Abeta clearance. We have investigated the expression of somatostatin in the anterior olfactory nucleus of AD and control brain. We report that somatostatin levels were reduced by approximately 50% in AD brain. Furthermore, triple-immunofluorescence revealed co-localization of somatostatin expression with Abeta (65.43%) with Abeta and tau (19.75%) and with tau (2.47%). These data indicate that somatostatin decreases in AD and its expression may be linked with Abeta deposition.

Chemical stimuli are sensed through the olfactory and vomeronasal epithelia, and the sensory cells of both systems undergo neuronal turnover during adulthood. In the vomeronasal epithelium, stem cells adjacent to the basal lamina divide and migrate to replace two classes of sensory neurons: apical neurons that express G(i2alpha)-linked V1R vomeronasal receptors and project to the anterior accessory olfactory bulb, and basal neurons that express G(oalpha)-linked V2R receptors and project to the posterior accessory olfactory bulb. Most of the dividing cells are present in the margins of the epithelium and only migrate locally. Previous studies have suggested that these marginal cells may participate in growth, sensory cell replacement or become apoptotic before maturation; however, the exact fate of these cells have remained unclear. In this work we investigated the fate of these marginal cells by analyzing markers of neurogenesis (bromodeoxyuridine incorporation), apoptosis (caspase-3), and neuronal maturation (olfactory marker protein and Neurotrace Nissl stain). Our data reveal a pool of dividing cells in the epithelial margins that predominantly give rise to mature neurons and only rarely undergo apoptosis. Newly generated cells are several times more numerous than apoptotic cells. These marginal neuroblasts could therefore constitute a net neural addition zone during adulthood.

The vomeronasal system is segregated from the epithelium to the bulb. Two classes of receptor neurons are apically and basally placed in the vomeronasal epithelium, express Gi2alpha and Goalpha proteins and V1R and V2R receptors and project to the anterior and posterior portions of the accessory olfactory bulb, respectively. Apart from common vomeronasal recipient structures in the amygdala, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala. The efferent projections from these two amygdaloid structures to the hypothalamus were investigated. These two vomeronasal subsystems mediated by V1R and V2R receptors were partially segregated, not only in amygdala, but also in the hypothalamus.

Projections from the olfactory bulbs have been traditionally described as 'nontopographically organized'. Olfactory and vomeronasal projections have been reported to reach nonoverlapping cortical areas. Four receptor expression zones have been described in the olfactory epithelium, maintained in the main olfactory bulb, but none in the olfactory cortex. Recent data have demonstrated convergence in the basal telencephalon of olfactory and vomeronasal projections. Injections of methanesulfonate hydroxystilbamidine (FluoroGold) in the chemosensory cortex were done to map retrograde labeling in the bulbs. Topography was not observed in the four zones of the main olfactory bulb. Areas of the rostral telencephalon were shown to receive simultaneous inputs from the main and accessory olfactory bulbs.

Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients.The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed.In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus.The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society.

The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.

New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto twenty-one-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.

Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α-synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co-localisation of these markers with α-synuclein was performed. Triple labeling of calbindin, somatostatin and α-synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α-Synuclein-positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non-significant increase over time from 16 to 30-43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α-Synuclein mostly co-localised with calbindin and a number of these cells also co-expressed somatostatin. These data on α-synucleinopathy staging in the amygdala could help to explain non-motor symptoms as well as to understand the progression of Parkinson's disease in the brain.

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, resting tremor, and postural instability. Neuropathologically, intracellular aggregates of α-synuclein in Lewy bodies and Lewy neurites appear in particular brain areas according to a sequence of stages. Clinical diagnosis is usually established when motor symptoms are evident (corresponding to Braak stage III or later), years or even decades after onset of the disease. Research at early stages is therefore essential to understand the etiology of PD and improve treatment. Although classically considered as a motor disease, non-motor symptoms have recently gained interest. Olfactory deficits are among the earliest non-motor features of PD. Interestingly, α-synuclein deposits are present in the olfactory bulb and anterior olfactory nucleus at Braak stage I. Several lines of evidence have led to proposals that PD pathology spreads by a prion-like mechanism via the olfactory and vagal systems to the substantia nigra. In this context, current data on the temporal appearance of α-synuclein aggregates in the olfactory system of both humans and transgenic mice are of particular relevance. In addition to the proposed retrograde nigral involvement via brainstem nuclei, olfactory pathways could potentially reach the substantia nigra, and the possibility of centrifugal progression warrants investigation. This review analyzes the involvement of α-synuclein in different elements of the olfactory system, in both humans and transgenic models, from the hodological perspective of possible anterograde and/or retrograde progression of this proteinopathy within the olfactory system and beyond-to the substantia nigra and the remainder of the central and peripheral nervous systems.

Impaired olfaction has been described as an early symptom of Alzheimer's disease. Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Interestingly, neuropathology begins in the transentorhinal cortex and extends to the neighboring limbic system and basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus and olfactory bulb. The human piriform cortex has been described as a crucial area in odor quality coding; disruption of this region mediates early olfactory deficits in Alzheimer's disease. Most neuropathological investigations have focused on the entorhinal cortex and hippocampus, whereas the piriform cortex has largely been neglected. This work aims to characterize the expression of the neuropathological amyloid-β peptide, tau protein and interneuron population markers (calretinin, parvalbumin and somatostatin) in the piriform cortex of ten Alzheimer-diagnosed (80.4 ± 8.3 years old) and five control (69.6 ± 11.1) cases. Here, we examined the distribution of different interneuronal markers as well as co-localization of interneurons and pathological markers. Results indicated preferential vulnerability of somatostatin- (p = 0.0001 < α = 0.05) and calretinin-positive (p = 0.013 < α = 0.05) cells that colocalized with amyloid-β peptide, while the prevalence of parvalbumin-positive cells was increased (p = 0.045 < α = 0.05) in the Alzheimer's cases. These data may help to reveal the neural basis of olfactory deficits linked to Alzheimer's disease as well as to characterize neuronal populations preferentially vulnerable to neuropathology in regions critically involved in early stages of the disease.

Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta-amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder.

At the beginning of twenty century Alois Alzheimer described the pathology that now bears his name (Alzheimer, 1907). Over a hundred years later, Alzheimer’s disease (AD) is the most common cause of dementia in developed countries. Here eighteen million people are currently affected and the number of patients is expected to increase dramatically with the ongoing increase in the elderly population (Fotuhi et al., 2009, Mount & Downton, 2006). Because no suitable biomarkers are available, the diagnosis of AD remains inconclusive until postmortem pathological analysis, and physicians rely on behavioral manifestations to differentiate between AD and other conditions. For this reason firm diagnosis is generally only made at later stages of the disorder when treatment is purely palliative. These features make AD a social and economic challenge in developed countries (Wimo et al., 2010). Clinically, AD is characterized by progressive loss of cognitive functions with specific deficits in episodic memory. Clinical diagnosis of is generally only made when cognitive deficits are sufficiently severe to cause dependent status of the patient (Nestor et al., 2004). Pathological analyses of AD brain have described two distinct types of proteinopathy in the frontal and temporal lobes involving the limbic system and the basal forebrain. The first type comprises aggregates of beta-amyloid peptide (Aβ) – a specific fragment of the amyloid precursor protein (APP), a plasma membrane protein. These aggregates accumulate in the extracellular space and give rise to senile plaques (SPs). SPs cause synaptotoxicity, neurotoxicity, oxidative stress and hypoxia (Peers et al., 2009, Selkoe, 2001, 2008). The second proteinopathy occurs in the cytosol. Hyperphosphorylation and abnormal aggregation of the microtubule-associated protein tau leads to the intracellular formation of neurofibrillary tangles (NFTs) which cause cytoskeleton destabilization and eventually cell death (Hernandez & Avila, 2008, Selkoe, 2001). It has been widely reported that olfactory loss (anosmia and hyposmia) takes place in the early stages of AD, and before any detectable cognitive deficits are present. Interestingly, AD pathology extends throughout the limbic system and the basal forebrain, including the olfactory system (Braak & Braak, 1991). The human olfactory system includes peripheral sensory neurons in the olfactory epithelium; these send their axons across the cribriform plate of the etmoides bone to the olfactory bulbs. In the glomerular layer of the olfactory

Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

Impaired olfaction is an early symptom of Parkinson's disease. The underlying neuropathology likely includes alpha-synucleinopathy in the olfactory bulb at an earlier stage (Braak's stage1) than pathology in the substantia nigra, which is not observed until stage 3. In this report, we investigated the distribution and cell types affected by alpha-synuclein in the olfactory bulb of transgenic mice (2-8 months of age) expressing the human A53T variant of alpha-synuclein. alpha-Synuclein immunostaining progressively affects interneurons and mitral cells. Double labeling studies demonstrate that dopaminergic cells are hardly involved, whereas glutamatergic- and calcium binding protein-positive cells are severely affected. This temporal evolution and the cell types expressing alpha-synuclein are reminiscent of idiopathic Parkinson's disease and support the usefulness of this model to address specific topics in the premotor phase of the disease.

Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.

The hippocampal formation is anatomically and functionally related to the olfactory structures especially in rodents. The entorhinal cortex (EC) receives afferent projections from the main olfactory bulb; this constitutes an olfactory pathway to the hippocampus. In addition to the olfactory system, most mammals possess an accessory olfactory (or vomeronasal) system. The relationships between the hippocampal formation and the vomeronasal system are virtually unexplored. Recently, a centrifugal projection from CA1 to the accessory olfactory bulb has been identified using anterograde tracers. In the study reported herein, experiments using anterograde tracers confirm this projection, and injections of retrograde tracers show the distribution and morphology of a population of CA1 and ventral subicular neurons projecting to the accessory olfactory bulb of rats. These results extend previous descriptions of hippocampal projections to the accessory olfactory bulb by including the ventral subiculum and characterizing the morphology, neurochemistry (double labeling with somatostatin), and distribution of such neurons. These data suggest feedback hippocampal control of chemosensory stimuli in the accessory olfactory bulb. Whether this projection processes spatial information on conspecifics or is involved in learning and memory processes associated with chemical stimuli remains to be elucidated. © 2008 Wiley-Liss, Inc.