Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
2.
Mol Psychiatry ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969716

RESUMEN

Serotonergic psychedelics have potential therapeutic effects in treating anxiety and mood disorders, often after a single dose, and are suggested to have plasticity-inducing action. However, a comprehensive mechanism of action is still lacking. Here, we investigated how a single dose of the short-acting 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) acts on gene expression from microdissected brain regions (anterior cingulate cortex - ACC; basolateral amygdala - BLA; ventral hippocampus CA1 region - vCA1 and dentate gyrus-DG) of naive and stressed mice. Specifically, we compared gene expression of Arc, Zif268, BDNF, CREB, mTORC1, NR2A, TRIP8b, and NFkB in mice injected with 5-MeO-DMT or saline at different time points (1 h, 5 h, or 5 days prior). 5-MeO-DMT altered mRNA expression of immediate early genes Arc and ZiF268 in the ACC, BLA, and vCA1, while NR2A expression was decreased after 5 h in the vCA1. We also found a long-term increase in TRIP8b, a gene related to the modulation of neuronal activity, in the vCA1 after 5 days. Behaviorally, 5-MeO-DMT treated mice showed mixed anxiolytic and anxiogenic effects in the elevated plus maze and open field test 24 h or 5 days after treatment. However, pre-treated mice subjected to acute stress showed both lower corticosterone levels and robust anxiolytic effects of 5-MeO-DMT administration. Together, our findings provide insights into the molecular actions of 5-MeO-DMT in the brain related to anxiolytic effects of behavior.

3.
Curr Opin Insect Sci ; : 101230, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971524

RESUMEN

We often consider mosquitoes through an 'anthropocentric lens' that disregards their interactions with non-human and non-pathogenic organisms, even though these interactions can be harnessed for mosquito control. Mosquitoes have been recognized as floral visitors, and pollinators, for more than a century. However, we know relatively little about mosquito-plant interactions, excepting some nutrition and chemical ecology-related topics, compared to mosquito-host interactions, and frequently use flawed methodology when investigating them. Recent work demonstrates mosquitoes use multimodal sensory cues to locate flowers, including ultraviolet visual cues, and we may underestimate mosquito pollination. This review focuses on current knowledge of how mosquitoes locate flowers, floral visitation assay methodology, mosquito pollination, and implications for technologies such as sterile male mosquito release through genetic control programs or Wolbachia infection.

4.
Sci Rep ; 14(1): 11281, 2024 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760450

RESUMEN

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20-50 Hz) and mid (50-100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.


Asunto(s)
Hipocampo , Corteza Prefrontal , Sueño , Vigilia , Animales , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Ratas , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Vigilia/efectos de los fármacos , Vigilia/fisiología , Masculino , Sueño/efectos de los fármacos , Sueño/fisiología , Electroencefalografía , Ritmo Teta/efectos de los fármacos , Alucinógenos/farmacología
5.
Artículo en Inglés | MEDLINE | ID: mdl-38160852

RESUMEN

BACKGROUND: Psychiatric disorders, such as schizophrenia, are complex and challenging to study, partly due to the lack of suitable animal models. However, the absence of the Slc10a4 gene, which codes for a monoaminergic and cholinergic associated vesicular transporter protein, in knockout mice (Slc10a4-/-), leads to the accumulation of extracellular dopamine. A major challenge for studying schizophrenia is the lack of suitable animal models that accurately represent the disorder. We sought to overcome this challenge by using Slc10a4-/- mice as a potential model, considering their altered dopamine levels. This makes them a potential animal model for schizophrenia, a disorder known to be associated with altered dopamine signaling in the brain. METHODS: The locomotion, auditory sensory filtering and prepulse inhibition (PPI) of Slc10a4-/- mice were quantified and compared to wildtype (WT) littermates. Intrahippocampal electrodes were used to record auditory event-related potentials (aERPs) for quantifying sensory filtering in response to paired-clicks. The channel above aERPs phase reversal was chosen for reliably comparing results between animals, and aERPs amplitude and latency of click responses were quantified. WT and Slc10a4-/- mice were also administered subanesthetic doses of ketamine to provoke psychomimetic behavior. RESULTS: Baseline locomotion during auditory stimulation was similar between Slc10a4-/- mice and WT littermates. In WT animals, normal auditory processing was observed after i.p saline injections, and it was maintained under the influence of 5 mg/kg ketamine, but disrupted by 20 mg/kg ketamine. On the other hand, Slc10a4-/- mice did not show significant differences between N40 S1 and S2 amplitude responses in saline or low dose ketamine treatment. Auditory gating was considered preserved since the second N40 peak was consistently suppressed, but with increased latency. The P80 component showed higher amplitude, with shorter S2 latency under saline and 5 mg/kg ketamine treatment in Slc10a4-/- mice, which was not observed in WT littermates. Prepulse inhibition was also decreased in Slc10a4-/- mice when the longer interstimulus interval of 100 ms was applied, compared to WT littermates. CONCLUSION: The Slc10a4-/- mice responses indicate that cholinergic and monoaminergic systems participate in the PPI magnitude, in the temporal coding (response latency) of the auditory sensory gating component N40, and in the amplitude of aERPs P80 component. These results suggest that Slc10a4-/- mice can be considered as potential models for neuropsychiatric conditions.


Asunto(s)
Dopamina , Ketamina , Animales , Humanos , Ratones , Estimulación Acústica/métodos , Percepción Auditiva , Colinérgicos , Dopamina/fisiología , Potenciales Evocados Auditivos/fisiología , Filtrado Sensorial
6.
Curr Protoc ; 2(7): e457, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35822833

RESUMEN

Laser Capture Microdissection (LCM) is a method that allows one to select and dissect well-defined structures, specific cell subpopulations, or even single cells from different types of tissue for subsequent extraction of DNA, RNA, or proteins. Its precision allows the dissection of specific groups of cells, avoiding unwanted cells. However, despite its efficiency, several steps can affect the sample RNA integrity. RNA instability represents a challenge in the LCM method, and low RNA integrity can introduce biases, as different transcripts often have different degradation rates. Here we describe an optimized protocol to provide good-concentration and high-quality RNA from specific structures: dentate gyrus and CA1 in the hippocampus, basolateral amygdala, and anterior cingulate cortex of mouse brain tissue. However, the protocol is applicable to other areas of interest. © 2022 Wiley Periodicals LLC. Basic Protocol: Laser capture microdissection of mouse brain tissue.


Asunto(s)
Encéfalo , ARN , Animales , Captura por Microdisección con Láser/métodos , Ratones , ARN/genética , Estabilidad del ARN
7.
BMC Biol ; 20(1): 102, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35550106

RESUMEN

BACKGROUND: The dorsal cochlear nucleus (DCN) is a region known to integrate somatosensory and auditory inputs and is identified as a potential key structure in the generation of phantom sound perception, especially noise-induced tinnitus. Yet, how altered homeostatic plasticity of the DCN induces and maintains the sensation of tinnitus is not clear. Here, we chemogenetically decrease activity of a subgroup of DCN neurons, Ca2+/Calmodulin kinase 2 α (CaMKII α)-positive DCN neurons, using Gi-coupled human M4 Designer Receptors Exclusively Activated by Designer Drugs (hM4Di DREADDs), to investigate their role in noise-induced tinnitus. RESULTS: Mice were exposed to loud noise (9-11kHz, 90dBSPL, 1h, followed by 2h of silence), and auditory brainstem responses (ABRs) and gap prepulse inhibition of acoustic startle (GPIAS) were recorded 2 days before and 2 weeks after noise exposure to identify animals with a significantly decreased inhibition of startle, indicating tinnitus but without permanent hearing loss. Neuronal activity of CaMKII α+ neurons expressing hM4Di in the DCN was lowered by administration of clozapine-N-oxide (CNO). We found that acutely decreasing firing rate of CaMKII α+ DCN units decrease tinnitus-like responses (p = 3e -3, n = 11 mice), compared to the control group that showed no improvement in GPIAS (control virus; CaMKII α-YFP + CNO, p = 0.696, n = 7 mice). Extracellular recordings confirmed CNO to decrease unit firing frequency of CaMKII α-hM4Di+ mice and alter best frequency and tuning width of response to sound. However, these effects were not seen if CNO had been previously administered during the noise exposure (n = 6 experimental and 6 control mice). CONCLUSION: We found that lowering DCN activity in mice displaying tinnitus-related behavior reduces tinnitus, but lowering DCN activity during noise exposure does not prevent noise-induced tinnitus. Our results suggest that CaMKII α-positive cells in the DCN are not crucial for tinnitus induction but play a significant role in maintaining tinnitus perception in mice.


Asunto(s)
Núcleo Coclear , Acúfeno , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Núcleo Coclear/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Ratones , Percepción , Acúfeno/etiología
8.
Semin Immunopathol ; 44(4): 461-474, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35641679

RESUMEN

Autoimmune liver diseases (AILD) include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These immune-mediated liver diseases involve a break down in peripheral self-tolerance with largely unknown aetiology. Regulatory T cells (Treg) are crucial in maintaining immunological tolerance. Hence, Treg immunotherapy is an attractive therapeutic option in AILD. Currently, AILD do not have a curative treatment option and patients take life-long immunosuppression or bile acids to control hepatic or biliary inflammation. Clinical investigations using good manufacturing practice (GMP) Treg in autoimmune liver disease have thus far demonstrated that Treg therapy is safe and that Treg migrate to inflamed liver tissue. For Treg immunotherapy to achieve efficacy in AILD, Treg must be retained within the liver and maintain their suppressive phenotype to dampen ongoing immune responses to hepatocytes and biliary epithelium. Therefore, therapeutic Treg subsets should be selected for tissue residency markers and maximal functionality. Optimisation of dosing regime and understanding longevity of Treg in vivo are critical to successful Treg therapy. It is also essential to consider combination therapy options to complement infused Treg, for instance low-dose interleukin-2 (IL-2) to support pre-existing and infused Treg survival and suppressive function. Understanding the hepatic microenvironment in both early- and late-stage AILD presents significant opportunity to better tailor Treg therapy in different patient groups. Modification of a hostile microenvironment to a more favourable one either prior to or during Treg therapy could enhance the efficacy and longevity of infused GMP-Treg. Applying recent technology to discovery of autoantigen responses in AILD, T cell receptor (TCR) sequencing and use of chimeric antigen receptor (CAR) technology represents the next frontier for disease-specific CAR-Treg therapies. Consideration of all these aspects in future trials and discovery research would position GMP Treg immunotherapy as a viable personalised-medicine treatment option for effective control of autoimmune liver diseases.


Asunto(s)
Enfermedades Autoinmunes , Colangitis Esclerosante , Hepatitis Autoinmune , Hepatopatías , Enfermedades Autoinmunes/terapia , Colangitis Esclerosante/terapia , Humanos , Hepatopatías/etiología , Hepatopatías/terapia , Linfocitos T Reguladores
9.
eNeuro ; 8(1)2021.
Artículo en Inglés | MEDLINE | ID: mdl-33563600

RESUMEN

The dorsal cochlear nucleus (DCN) is a region of particular interest for auditory and tinnitus research. However, lack of useful genetic markers for in vivo manipulations hinders elucidation of the DCN contribution to tinnitus pathophysiology. This work assesses whether adeno-associated viral vectors (AAV) containing the calcium/calmodulin-dependent protein kinase 2α (CaMKIIα) promoter and a mouse line of nicotinic acetylcholine receptor α2 subunit (Chrna2)-Cre can target specific DCN populations. We found that CaMKIIα cannot be used to target excitatory fusiform DCN neurons as labeled cells showed diverse morphology indicating they belong to different classes of DCN neurons. Light stimulation after driving Channelrhodopsin2 (ChR2) by the CaMKIIα promoter generated spikes in some units but firing rate decreased when light stimulation coincided with sound. Expression and activation of CaMKIIα-eArchaerhodopsin3.0 in the DCN produced inhibition in some units but sound-driven spikes were delayed by concomitant light stimulation. We explored the existence of Cre+ cells in the DCN of Chrna2-Cre mice by hydrogel embedding technique (CLARITY). There were almost no Cre+ cell bodies in the DCN; however, we identified profuse projections arising from the ventral cochlear nucleus (VCN). Anterograde labeling in the VCN revealed projections to the ipsilateral superior olive and contralateral medial nucleus of the trapezoid body (MNTB; bushy cells), and a second bundle terminating in the DCN, suggesting the latter to be excitatory Chrna2+ T-stellate cells. Exciting Chrna2+ cells increased DCN firing. This work shows that cortical molecular tools may be useful for manipulating the DCN especially for tinnitus studies.


Asunto(s)
Núcleo Coclear , Acúfeno , Animales , Ratones , Neuronas , Sonido , Núcleos Vestibulares
10.
Artículo en Inglés | MEDLINE | ID: mdl-32116619

RESUMEN

Optogenetics is revolutionizing Neuroscience, but an often neglected effect of light stimulation of the brain is the generation of heat. In extreme cases, light-generated heat kills neurons, but mild temperature changes alter neuronal function. To date, most in vivo experiments rely on light stimulation of neural tissue using fiber-coupled lasers of various wavelengths. Brain tissue is irradiated with high light power that can be deleterious to neuronal function. Furthermore, absorbed light generates heat that can lead to permanent tissue damage and affect neuronal excitability. Thus, light alone can generate effects in neuronal function that are unrelated to the genuine "optogenetic effect." In this work, we perform a theoretical analysis to investigate the effects of heat transfer in rodent brain tissue for standard optogenetic protocols. More precisely, we first use the Kubelka-Munk model for light propagation in brain tissue to observe the absorption phenomenon. Then, we model the optothermal effect considering the common laser wavelengths (473 and 593 nm) used in optogenetic experiments approaching the time/space numerical solution of Pennes' bio-heat equation with the Finite Element Method. Finally, we then modeled channelrhodopsin-2 in a single and spontaneous-firing neuron to explore the effect of heat in light stimulated neurons. We found that, at commonly used light intensities, laser radiation considerably increases the temperature in the surrounding tissue. This effect alters action potential size and shape and causes an increase in spontaneous firing frequency in a neuron model. However, the shortening of activation time constants generated by heat in the single firing neuron model produces action potential failures in response to light stimulation. We also found changes in the power spectrum density and a reduction in the time required for synchronization in an interneuron network model of gamma oscillations. Our findings indicate that light stimulation with intensities used in optogenetic experiments may affect neuronal function not only by direct excitation of light sensitive ion channels and/or pumps but also by generating heat. This approach serves as a guide to design optogenetic experiments that minimize the role of tissue heating in the experimental outcome.

11.
Exp Neurol ; 326: 113175, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31923390

RESUMEN

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.


Asunto(s)
Envejecimiento/psicología , Ansiedad/inducido químicamente , Ansiedad/psicología , Alucinógenos/uso terapéutico , Metoxidimetiltriptaminas/uso terapéutico , Salicilatos , Animales , Ansiedad/prevención & control , Conducta Animal , Electroencefalografía/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva Provocada por Ruido/complicaciones , Hipocampo/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Microelectrodos , Actividad Motora , Corteza Prefrontal/fisiopatología , Salicilatos/antagonistas & inhibidores , Acúfeno/inducido químicamente , Acúfeno/fisiopatología , Acúfeno/psicología
12.
Sci Rep ; 9(1): 19164, 2019 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-31844150

RESUMEN

Noise pollution is increasing globally, and as oceans are excellent conductors of sound, this is a major concern for marine species reliant on sound for key life functions. Loud, impulsive sounds from seismic surveys have been associated with impacts on many marine taxa including mammals, crustaceans, cephalopods, and fish. However, impacts across large spatial scales or multiple species are rarely considered. We modelled over 8,000 hours of cetacean survey data across a large marine ecosystem covering > 880,000 km2 to investigate the effect of seismic surveys on baleen and toothed whales. We found a significant effect of seismic activity across multiple species and habitats, with an 88% (82-92%) decrease in sightings of baleen whales, and a 53% (41-63%) decrease in sightings of toothed whales during active seismic surveys when compared to control surveys. Significantly fewer sightings of toothed whales also occurred during active versus inactive airgun periods of seismic surveys, although some species-specific response to noise was observed. This study provides strong evidence of multi-species impacts from seismic survey noise on cetaceans. Given the global proliferation of seismic surveys and large propagation distances of airgun noise, our results highlight the large-scale impacts that marine species are currently facing.

13.
Hippocampus ; 29(12): 1224-1237, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31301163

RESUMEN

The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2-cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike-frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization-activated current (Ih ) compared to ventral OLM cells. Immunohistochemical examination indicates the h-current to correspond to hyperpolarization-activated cyclic nucleotide-gated subunit 2 (HCN2) channels. Computational studies suggest that Ih in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.


Asunto(s)
Potenciales de Acción/fisiología , Hipocampo/fisiología , Interneuronas/fisiología , Potenciales de la Membrana/fisiología , Receptores Nicotínicos/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Transgénicos
15.
J Neurochem ; 149(4): 471-487, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30828804

RESUMEN

Locus coeruleus (LC) is the name of a group of large sized neurons located at the brain stem, which provides the main source of noradrenaline to the central nervous system, virtually, innervating the whole brain. All noradrenergic signalling provided by this nucleus is dependent on an intrinsic pacemaker process. Our study aims to understand how noradrenergic neurons finely tune their pacemaker processes and regulate their activities. Here we present that mitochondrial perturbation in the LC from mice, inhibits spontaneous firing by a hyperpolarizing response that involves Ca2+ entry via L-type Ca2+ channels and the actin cytoskeleton. We found that pharmacological perturbation of mitochondria from LC neurons using the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), induced a dominant hyperpolarizing response when electrophysiological approaches were performed. Surprisingly, the CCCP-induced hyperpolarizing response was dependent on L-type Ca2+ channel-mediated Ca2+ entry, as it was inhibited by: the removal of extracellular Ca2+ ; the addition of Cd2+ ; nifedipine or nicardipine; but not by the intracellular dialysis with the Ca2+ chelator 1,2-Bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, the latter indicating that the response was not because of a global change in [Ca2+ ]c but does not exclude action at intracellular microdomains. Further to this, the incubation of slices with cytochalasin D, an agent that depolymerises the actin cytoskeleton, inhibited the hyperpolarizing response indicating an involvement of the actin cytoskeleton. The data are consistent with the hypothesis that there is a crosstalk between mitochondria and L-type Ca2+ channels leading to modulation of noradrenergic neuronal activity mediated by the actin cytoskeleton. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Neuronas Adrenérgicas/metabolismo , Canales de Calcio Tipo L/metabolismo , Locus Coeruleus/metabolismo , Mitocondrias/metabolismo , Animales , Células Cultivadas , Femenino , Masculino , Ratones
16.
Hippocampus ; 29(8): 755-761, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30767318

RESUMEN

Prolonged increases in excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes, and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 hr of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Finally, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.


Asunto(s)
Potenciales de Acción/fisiología , Espinas Dendríticas/fisiología , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Animales , Ratones , Neuronas/fisiología , Optogenética , Sinapsis/fisiología
17.
Hippocampus ; 29(1): 15-25, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30152905

RESUMEN

Salicylate intoxication is a cause of tinnitus in humans and it is often used to produce tinnitus-like perception in animal models. Here, we assess whether salicylate induces anxiety-like electrophysiological and behavioral signs. Using microwire electrode arrays, we recorded local field potential in the ventral and, in some experiments dorsal hippocampus, in an open field arena 1 hr after salicylate (300 mg/kg) injection. We found that animals treated with salicylate moved dramatically less than saline treated animals. Salicylate-treated animals showed a strong 4-6 Hz (type 2) oscillation in the ventral hippocampus (with smaller peaks in dorsal hippocampus electrodes). Coherence in the 4-6 Hz-theta band was low in the ventral and dorsal hippocampus when compared to movement-related theta coherence (7-10 Hz). Moreover, movement related theta oscillation frequency decreased and its dependency on running speed was abolished. Our results suggest that salicylate-induced theta is mostly restricted to the ventral hippocampus. Slow theta has been classically associated to anxiety-like behaviors. Here, we show that salicylate application can consistently generate low frequency theta in the ventral hippocampus. Tinnitus and anxiety show strong comorbidity and the increase in ventral hippocampus low frequency theta could be part of this association.


Asunto(s)
Ansiedad/inducido químicamente , Ansiedad/psicología , Hipocampo/efectos de los fármacos , Carrera/psicología , Salicilatos/toxicidad , Ritmo Teta/efectos de los fármacos , Animales , Hipocampo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Carrera/fisiología , Ritmo Teta/fisiología
18.
Front Mol Neurosci ; 11: 312, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30233313

RESUMEN

The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

19.
Nat Commun ; 9(1): 3638, 2018 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-30194386

RESUMEN

Dorsal and ventral hippocampus regions exert cognition and emotion-related functions, respectively. Since both regions display rhythmic activity, specific neural oscillatory pacemakers may underlie their functional dichotomy. Type 1 theta oscillations are independent of cholinergic transmission and are observed in the dorsal hippocampus during movement and exploration. In contrast, type 2 theta depends on acetylcholine and appears when animals are exposed to emotionally laden contexts such as a predator presence. Despite its involvement in emotions, type 2 theta has not been associated with the ventral hippocampus. Here, we show that optogenetic activation of oriens-lacunosum moleculare (OLM) interneurons in the ventral hippocampus drives type 2 theta. Moreover, we found that type 2 theta generation is associated with increased risk-taking behavior in response to predator odor. These results demonstrate that two theta oscillations subtypes originate in the two hippocampal regions that predominantly underlie either cognitive or emotion-related functions.


Asunto(s)
Hipocampo/fisiología , Interneuronas/fisiología , Asunción de Riesgos , Ritmo Teta , Animales , Masculino , Ratones , Ratones Transgénicos , Odorantes , Optogenética , Receptores Nicotínicos/metabolismo
20.
Neuron ; 99(2): 404-412.e3, 2018 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-29983324

RESUMEN

Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor α2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set out to determine whether selective modulation of OLMα2 cells in the intermediate CA1 affects learning and memory in vivo. Our data show that intermediate OLMα2 cells can either enhance (upon their inhibition) or impair (upon their activation) object memory encoding in freely moving mice, thus exerting bidirectional control. Moreover, we find that OLMα2 cell activation inhibits fear-related memories and that OLMα2 cells respond differently to nicotine in the dorsoventral axis. These results suggest that intermediate OLMα2 cells are an important component in the CA1 microcircuit regulating learning and memory processes. VIDEO ABSTRACT.


Asunto(s)
Reacción de Prevención/fisiología , Región CA1 Hipocampal/citología , Región CA1 Hipocampal/fisiología , Receptores Nicotínicos/biosíntesis , Animales , Región CA1 Hipocampal/química , Femenino , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores Nicotínicos/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...