A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor.

Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains.IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.

Study of duodenal bacterial communities by 16S rRNA gene analysis in adults with active celiac disease vs non-celiac disease controls.

AIMS: Several studies have suggested that abnormalities in the small-intestinal microbiota might be involved in the development or the pathogenesis of celiac disease (CD). The objective of this study was to characterize and compare the composition of the duodenal microbiota between CD patients and non-CD controls. METHOD AND RESULTS: Bacterial communities were identified by pyrosequencing of 16S rRNA extracted from duodenal biopsies. The sequences analysis showed that the majority of the reads were classified within two phyla: Firmicutes and Proteobacteria. Bacterial richness and diversity were higher in non-CD controls than in untreated CD patients, but the differences were not statistically significant. The principal coordinates analysis revealed that bacterial communities of non-CD controls and untreated CD patients were dispersed without forming a clear group according to diagnosis of CD. CONCLUSIONS: There are no statistically significant differences in the upper small intestinal composition of bacterial communities between untreated CD patients and non-CD controls. SIGNIFICANCE AND IMPACT OF THE STUDY: This pyrosequencing analysis reveals a global picture of the duodenal microbiota that could be useful in future trials investigating the role of the microbiota in CD.

Links between headaches and epilepsy: current knowledge and terminology.

INTRODUCTION AND OBJECTIVES: Headaches (including migraines) and epilepsy have a high level of comorbidity and may be confused during diagnosis. Although physicians have known for centuries that these two conditions are somehow linked, their relationship remains poorly understood. Herein we describe the known associations between them, their underlying physiopathologic and genetic mechanisms, and the treatments recommended for them. METHOD: We have reviewed the most relevant publication of headache/migraine and epilepsy by using the PubMed data base. DESCRIPTION: An individual can suffer both from headaches (either migraine and/or other type of headache) and epilepsy, either by chance or because of a common underlying pathology. In these cases, the headache usually occurs at a different moment than the seizure ("interictal headache"). However, headaches sometimes occur simultaneously with, or very close in time to, the seizure: one that occurs at the same time as an epileptic seizure is known as an "ictal epileptic headache" or as "hemicrania epileptica"; one that precedes a seizure is known as a "pre-ictal headache"; and one that follows a seizure is known as a "post-ictal headache". There is a particular type of pre-ictal headache, known as "migralepsy", which occurs during or just after a migraine aura. CONCLUSIONS: The terminology and concepts employed to describe possible associations between headaches (mainly migraines) and epilepsy have evolved over time with increasing clinical and physiopathogenic knowledge. Some researchers have suggested eliminating the term migralepsy and using the terms ictal epileptic headache and hemicrania epileptica exclusively and uniformly in all classification systems.

Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis.

BACKGROUND: Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis. OBJECTIVE: The objective of this study was to investigate the role of plasma CHI3L1 in MS clinical course and disease activity and to evaluate the effect of interferon-beta (IFNß) treatment on protein levels. METHODS: Plasma CHI3L1 levels were determined by ELISA in 57 healthy controls (HC), 220 untreated MS patients [66 primary progressive MS patients (PPMS), 30 secondary progressive MS patients (SPMS), and 124 relapsing-remitting MS patients (RRMS), 94 during clinical remission and 30 during relapse], and 32 MS patients receiving IFNß treatment. A polymorphism of the CHI3L1 gene, rs4950928, was genotyped in 3274 MS patients and 3483 HC. RESULTS: Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC. CHI3L1 levels were similar between RRMS patients in relapse and remission. A trend towards decreased CHI3L1 levels was observed in IFNß-treated patients. Allele C of rs4950928 was significantly associated with PPMS patients and with higher plasma CHI3L1 levels. CONCLUSIONS: These findings point to a role of CHI3L1 in patients with progressive forms of MS, particularly in those with PPMS.

[Migraine as a cerebrovascular risk factor]. / Migraña como factor de riesgo cerebrovascular.

INTRODUCTION: Migraine has become an important vascular risk factor during the past few years, along with the presence of white matter and clinically silent ischaemic lesions. Whether these findings contribute to the migraine becoming chronic has been a source of debate. People with chronic migraine also have a less favourable metabolic profile. An exhaustive review of the literature has been made in order to try to clarify the relationship between migraine and vascular risk factors. DEVELOPMENT: Migraine, particularly with aura and in women < 45 years-old, is associated with an increased risk of cerebral infarction. This risk increases if the patient smokes or uses oral contraceptives. Migraine can also be a direct cause of a stroke, although it is an infrequent complication. Migraine with aura is associated with a risk factor of 12 of having subclinical infarctions in posterior fossa circulation. CONCLUSIONS: Since migraine is an independent vascular risk factor, a better control of migraine attacks, as well as other possible concomitant vascular risk factors, should decrease the likelihood of a stroke. Overall, the real risk of infarction is low, with 3.8 new cases per 100,000 women and year.

Role of tumour necrosis factor (TNF)-α and TNFRSF1A R92Q mutation in the pathogenesis of TNF receptor-associated periodic syndrome and multiple sclerosis.

It has long been known that tumour necrosis factor (TNF)/TNFRSF1A signalling is involved in the pathophysiology of multiple sclerosis (MS). Different genetic and clinical findings over the last few years have generated renewed interest in this relationship. This paper provides an update on these recent findings. Genome-wide association studies have identified the R92Q mutation in the TNFRSF1A gene as a genetic risk factor for MS (odds ratio 1·6). This allele, which is also common in the general population and in other inflammatory conditions, therefore only implies a modest risk for MS and provides yet another piece of the puzzle that defines the multiple genetic risk factors for this disease. TNFRSF1A mutations have been associated with an autoinflammatory disease known as TNF receptor-associated periodic syndrome (TRAPS). Clinical observations have identified a group of MS patients carrying the R92Q mutation who have additional TRAPS symptoms. Hypothetically, the co-existence of MS and TRAPS or a co-morbidity relationship between the two could be mediated by this mutation. The TNFRSF1A R92Q mutation behaves as a genetic risk factor for MS and other inflammatory diseases, including TRAPS. Nevertheless, this mutation does not appear to be a severity marker of the disease, neither modifying the clinical progression of MS nor its therapeutic response. An alteration in TNF/TNFRS1A signalling may increase proinflammatory signals; the final clinical phenotype may possibly be determined by other genetic or environmental modifying factors that have not yet been identified.

Generalized neck-shoulder hyperalgesia in chronic tension-type headache and unilateral migraine assessed by pressure pain sensitivity topographical maps of the trapezius muscle.

Spatial changes in pressure pain hypersensitivity are present throughout the cephalic region (temporalis muscle) in both chronic tension-type headache (CTTH) and unilateral migraine. The aim of this study was to assess pressure pain sensitivity topographical maps on the trapezius muscle in 20 patients with CTTH and 20 with unilateral migraine in comparison with 20 healthy controls in a blind design. For this purpose, a pressure algometer was used to assess pressure pain thresholds (PPT) over 11 points of the trapezius muscle: four points in the upper part of the muscle, two over the levator scapulae muscle, two in the middle part, and the remaining three points in the lower part of the muscle. Pressure pain sensitivity maps of both sides (dominant/non-dominant; symptomatic/non-symptomatic) were depicted for patients and controls. CTTH patients showed generalized lower PPT levels compared with both migraine patients (P = 0.03) and controls (P < 0.001). The migraine group had also lower PPT than healthy controls (P < 0.001). The most sensitive location for the assessment of PPT was the neck portion of the upper trapezius muscle in both patient groups and healthy controls (P < 0.001). PPT was negatively related to some clinical pain features in both CTTH and unilateral migraine patients (all P < 0.05). Side-to-side differences were found in strictly unilateral migraine, but not in those subjects with bilateral pain, i.e. CTTH. These data support the influence of muscle hyperalgesia in both CTTH and unilateral migraine patients and point towards a general pressure pain hyperalgesia of neck-shoulder muscles in headache patients, particularly in CTTH.

Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course.

The objectives of this study were: (1) to assess relative frequency of migraine in multiple sclerosis (MS) patients using the validated self-administered diagnostic questionnaire, and to compare the migraine rates in MS outpatients to age- and gender-matched historical population controls; (2) to compare clinical and radiographic characteristics in MS patients with migraine and headache-free MS patients. We conducted a cross-sectional study to assess the demographic profiles, headache features and clinical characteristics of MS patients attending a MS clinic using a questionnaire based on the American Migraine Prevalence and Prevention (AMPP) study. We compared the relative frequency of migraine in MS clinic patients and AMPP cohort. We also compared clinical and radiographic features in MS patients with migraine to an MS control group without headache. Among 204 MS patients, the relative frequency of migraine was threefold higher than in population controls both for women [55.7 vs. 17.1%; prevalence ratio (PR) =3.26, p<0.001] and men (18.4 vs. 5.6%; PR=3.29, p<0.001). In a series of logistic regression models that controlled for age, gender, disease duration, ß-interferon use, and depression, migraine in MS patients was significantly associated (p<0.01) with trigeminal and occipital neuralgia, facial pain, Lhermitte's sign, temporomandibular joint pain, non-headache pain and a past history of depression. Migraine status was not significantly associated with disability on patient-derived disability steps scale or T2 lesion burden on brain MRI. Migraine is three-times more common in MS clinic patients than in general population. MS-migraine group was more symptomatic than the MS-no headache group.

Nutritional profile of rodent diets impacts experimental reproducibility in microbiome preclinical research.

The lack of reproducibility of animal experimental results between laboratories, particularly in studies investigating the microbiota, has raised concern among the scientific community. Factors such as environment, stress and sex have been identified as contributors, whereas dietary composition has received less attention. This study firstly evaluated the use of commercially available rodent diets across research institutions, with 28 different diets reported by 45 survey respondents. Secondly, highly variable ingredient, FODMAP (Fermentable Oligo-, Di-, Mono-saccharides And Polyols) and gluten content was found between different commercially available rodent diets. Finally, 40 mice were randomized to four groups, each receiving a different commercially available rodent diet, and the dietary impact on cecal microbiota, short- and branched-chain fatty acid profiles was evaluated. The gut microbiota composition differed significantly between diets and sexes, with significantly different clusters in ß-diversity. Total BCFA were highest (p = 0.01) and SCFA were lowest (p = 0.03) in mice fed a diet lower in FODMAPs and gluten. These results suggest that nutritional composition of commercially available rodent diets impact gut microbiota profiles and fermentation patterns, with major implications for the reproducibility of results across laboratories. However, further studies are required to elucidate the specific dietary factors driving these changes.

Epicrania fugax: an ultrabrief paroxysmal epicranial pain.

Ten patients (one man and nine women, mean age 48.8 +/- 20.1) presented with a stereotypical and undescribed type of head pain. They complained of strictly unilateral, shooting pain paroxysms starting in a focal area of the posterior parietal or temporal region and rapidly spreading forward to the ipsilateral eye (n = 7) or nose (n = 3) along a lineal or zigzag trajectory, the complete sequence lasting 1-10 s. Two patients had ipsilateral lacrimation, and one had rhinorrhoea at the end of the attacks. The attacks could be either spontaneous or triggered by touch on the stemming area (n = 2), which could otherwise remain tender or slightly painful between the paroxysms (n = 5). The frequency ranged from two attacks per month to countless attacks per day, and the temporal pattern was either remitting (n = 5) or chronic (n = 5). This clinical picture might be a variant of an established headache or represent a novel syndrome.

[Determinants of prophylactic migraine therapy in Spain]. / Determinantes del uso de los fármacos con indicación para la profilaxis de la migrana en España.

INTRODUCTION: Migraine interferes with the quality of life of patients. Prophylactic medication is an option to be considered in cases showing inefficiency of symptomatic medication or an increase in the number of attacks. AIM: To evaluate the characteristics of patients that start on prophylactic treatment for migraine. PATIENTS AND METHODS: A multicenter epidemiologic survey was conducted in 110 neurological outpatient clinics and hospitals among adult patients of both sexes who required prophylactic treatment for migraine. Pain intensity was measured through a three-category scale: mild, moderate, or severe. Daily disability was measured by a disability questionnaire. RESULTS: A total of 735 patients with migraine who had started prophylactic treatment were considered valid for the analysis. The patients reported an average of 9.7 days with migraine in the previous month, 32% of the episodes lasting more than 24 hours. Half of the patients referred working or home disability due to migraine with a total average score of 15.1 on the disability scale (grade III). A 48% of the patients had previously received prophylactic treatment, the medications most commonly prescribed being flunarizine, propranolol and amitriptyline. At the study visit, the most commonly prescribed medications were topiramate, flunarizine, propranolol, and amitriptyline. CONCLUSIONS: Our study reveals that starting prophylactic treatment is in the majority of cases due to a high attack frequency. A clear evolution is being observed in prophylactic medication prescription, with a shift from flunarizine or propranolol to topiramate, which is prescribed more frequently nowadays.

Assessment of deep dynamic mechanical sensitivity in individuals with tension-type headache: The dynamic pressure algometry.

BACKGROUND: To explore the validity of dynamic pressure algometry for evaluating deep dynamic mechanical sensitivity by assessing its association with headache features and widespread pressure sensitivity in tension-type headache (TTH). METHODS: One hundred and eighty-eight subjects with TTH (70% women) participated. Deep dynamic sensitivity was assessed with a dynamic pressure algometry set (Aalborg University, Denmark© ) consisting of 11 different rollers including fixed levels from 500 g to 5300 g. Each roller was moved at a speed of 0.5 cm/s over a 60-mm horizontal line covering the temporalis muscle. Dynamic pain threshold (DPT-level of the first painful roller) was determined and pain intensity during DPT was rated on a numerical pain rate scale (NPRS, 0-10). Headache clinical features were collected on a headache diary. As gold standard, static pressure pain thresholds (PPT) were assessed over temporalis, C5/C6 joint, second metacarpal, and tibialis anterior muscle. RESULTS: Side-to-side consistency between DPT (r = 0.843, p < 0.001) and pain evoked (r = 0.712; p < 0.001) by dynamic algometer was observed. DPT was moderately associated with widespread PPTs (0.526 > r > 0.656, all p < 0.001). Furthermore, pain during DPT was negatively associated with widespread PPTs (-0.370 < r < -0.162, all p < 0.05). DISCUSSION: Dynamic pressure algometry was a valid tool for assessing deep dynamic mechanical sensitivity in TTH. DPT was associated with widespread pressure sensitivity independently of the frequency of headaches supporting that deep dynamic pressure sensitivity within the trigeminal area is consistent with widespread pressure sensitivity. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a new tool for assessing treatment effects. SIGNIFICANCE: The current study found that dynamic pressure algometry in the temporalis muscle was associated with widespread pressure pain sensitivity in individuals with tension-type headache. The association was independent of the frequency of headaches. Assessing deep static and dynamic somatic tissue pain sensitivity may provide new opportunities for differentiated diagnostics and possibly a tool for assessing treatment effects.

Face-to-Face or Telematic Cognitive Stimulation in Patients with Multiple Sclerosis and Cognitive Impairment: Why Not Both?

INTRODUCTION: Cognitive impairment (CI) affects 40-65% of patients with multiple sclerosis (MS). Few studies address telematic cognitive stimulation (TCS) in MS. The objective of this study is to evaluate the efficacy and impact of telestimulation or distance cognitive stimulation (TCS), with and without the support of face-to-face cognitive stimulation (FCS) in cognitive impairment in MS. METHODS: Multicentre, prospective, randomised, controlled study. We will include 98 MS patients with EDSS ≤ 6, symbol digit modality test (SDMT) ≤ Pc 25, and Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) > 26 points. Patients will be randomised into 3 groups, a TCS group, a mixed TCS/FCS group, and a control group. CS is performed 3 days a week for 3 months. Processing speed, memory, attention, and executive functions will be rehabilitated. FCS will include ecological exercises and strategies. EDSS and a cognitive evaluation (SDMT, CTMT, PASAT, and TAVEC), MSNQ, psychological impact scales (MSIS), and depression (BDI) will be carried out, baseline, postrehabilitation, and also 6 and 12 months later, to evaluate the effect of CS in the longer term. CONCLUSION: This study could help to establish the usefulness of TCS or, in its absence, TCS with face-to-face help for CI in MS. The interest lies in the clear benefits of remote rehabilitation in the daily life of patients.

Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing.

BACKGROUND: In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have yet to be determined. PURPOSE: Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer. METHODS: A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition (n = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served as a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests. RESULTS: The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P < .001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P < .01) and decreases in perceived benefits (P < .05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample. CONCLUSIONS: Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education may be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered.

SCN4A mutation as modifying factor of myotonic dystrophy type 2 phenotype.

In myotonic dystrophy type 2 (DM2), an association has been reported between early and severe myotonia and recessive chloride channel (CLCN1) mutations. No DM2 cases have been described with sodium channel gene (SCN4A) mutations. The aim is to describe a DM2 patient with severe and early onset myotonia and co-occurrence of a novel missense mutation in SNC4A. A 26-year-old patient complaining of hand cramps and difficulty relaxing her hands after activity was evaluated at our department. Neurophysiology and genetic analysis for DM1, DM2, CLCN1 and SCN4A mutations were performed. Genetic testing was positive for DM2 (2650 CCTG repeat) and for a variant c.215C>T (p.Pro72Leu) in the SCN4A gene. The variation affects the cytoplasmic N terminus domain of Nav1.4, where mutations have never been reported. The biophysical properties of the mutant Nav1.4 channels were evaluated by whole-cell voltage-clamp analysis of heterologously expressed mutant channel in tsA201 cells. Electrophysiological studies of the P72L variant showed a hyperpolarizing shift (-5 mV) of the voltage dependence of activation that may increase cell excitability. This case suggests that SCN4A mutations may enhance the myotonic phenotype of DM2 patients and should be screened for atypical cases with severe myotonia.

Awareness of heightened breast cancer risk among first-degree relatives of recently diagnosed breast cancer patients. The High Risk Breast Cancer Consortium.

This investigation had two goals: (a) to determine the proportion of first-degree relatives of recently diagnosed breast cancer patients who are unaware of their elevated risk for breast cancer; and (b) to identify demographic medical, and lifestyle factors that characterize these women. The ultimate objective was to identify women at increased risk who could benefit from breast cancer risk education. Three hundred ninety-five female first-degree relatives, ages 30-75 years, completed a structured telephone interview. Twenty-five % of these women believed that their risk for breast cancer was the "same as or lower than" women who do not have a family history of breast cancer, despite the fact that they had an objectively increased risk. Bivariate analyses revealed that women who were unmarried (chi2 = 14.8; P = 0.001) and had less than or equal to a high school education (chi2 = 9.2; P = 0.002) were significantly less likely to perceive themselves as being at increased risk for breast cancer. In addition, almost one-half of African-American women were unaware of their increased risk compared to only 19% of white women (chi2 = 29.9; P < 0.001). More smokers were unaware of their elevated risk compared to nonsmokers (43 versus 21%; chi2 = 15.1; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Numular headache: a coin-shaped cephalgia.

Numular headache is a chronic, mild to moderate, pressurelike pain in a circumscribed cranial area of approximately 2 to 6 cm in diameter. Pain usually is limited to the parietal region, although it may appear in any cranial site. It is a benign process of usually unknown origin.

Sexual dimorphism in accessory olfactory bulb mitral cells: a quantitative Golgi study.

The purpose of the present study was to identify the existence of sexual dimorphism in the dendritic field of accessory olfactory bulb mitral cells in rats and to investigate the effects of male orchidectomy and female androgenization on the day of birth upon this dendritic field. The rapid Golgi method was used to conduct a quantitative study of various characteristics of the dendritic field of accessory olfactory bulb mitral cells. The results indicated greater values for males than females for the following characteristics: (i) somatic area; (ii) degree of branching in the dendritic field; (iii) total dendritic length; and (iv) dendritic density around the neuronal soma. Orchidectomy of males, as well as androgenization of females, on the day of birth inverted these differences.

Neuronal plasticity in the hedgehog supraoptic nucleus during hibernation.

The purpose of the present study was to identify processes of plasticity in the receptive field of neurosecretory neurons of the supraoptic nucleus during hibernation in the hedgehog, in order to correlate them with the increased neurosecretory activity observed in this nucleus during this annual period. Using the Rapid Golgi method, a quantitative study was conducted in the receptive field of bipolar and multipolar neurons (the main components of the nucleus). Results indicate a generalized increase in the following characteristics: (1) number of dendritic spines per millimeter along the dendritic shafts; (2) degree of branching in the dendritic field; and (3) dendritic density around the neuronal soma. These data demonstrate modification of the dendritic field in the supraoptic nucleus during hibernation, a change undoubtedly related to functional conditions. Since the observed changes affect structures such as dendritic spines which are directly related to the arrival of neural afferences, the discussion is centered on the types of stimuli which may be responsible for the observed processes.