scholarly journals Cannabinoid CB1 Receptor-Dependent Long-Term Depression in Autaptic Excitatory Neurons

2009 ◽  
Vol 102 (2) ◽  
pp. 1160-1171 ◽  
Author(s):  
Ryan Kellogg ◽  
Ken Mackie ◽  
Alex Straiker
Keyword(s):  
Hippocampal Neurons ◽  
Single Neuron ◽  
Calcium Stores ◽  
Short Term ◽  
Long Term Depression ◽  
Erk Activation ◽  
Arachidonoyl Glycerol ◽  
The Brain ◽  
Cultured Hippocampal Neurons

Long-term depression (LTD) of synaptic signaling—lasting from tens of minutes to hours or longer—is a widespread form of synaptic plasticity in the brain. Neurons express diverse forms of LTD, including autaptic LTD (autLTD) observed in cultured hippocampal neurons, the mechanism of which remains unknown. We have recently reported that autaptic neurons express both endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) and metabotropic suppression of excitation (MSE). We now report that activating cannabinoid CB1 receptors is necessary for the induction of autLTD. Most surprisingly, CB1 does not induce autLTD via the Gi/o proteins typically activated by this receptor nor with Gs. Rather, the requirements of presynaptic phospholipase C and filled calcium stores suggest Gq. In autLTD, a 3- to 4-min activation of the receptor by the endocannabinoid 2-arachidonoyl glycerol leads to prolonged inhibition while leaving short-term inhibition (e.g., DSE) intact. autLTD requires activation of both metabo- and ionotropic glutamate receptors. autLTD also requires MEK/ERK activation. Under certain conditions, one or more DSE stimuli will elicit autLTD. It is becoming evident that cannabinoids mediate multiple forms of plasticity at a single synapse, stretching temporally from tens of seconds (DSE/MSE) to tens of minutes (autLTD) to hours (CB1 desensitization). Our findings imply a remarkable flexibility for the cannabinoid signaling system whereby discrete mechanisms of CB1 activation within a single neuron yield temporally and mechanistically distinct forms of plasticity.

scholarly journals Effects of silica nanoparticles on endolysosome function in primary cultured neurons

2019 ◽  
Vol 97 (4) ◽  
pp. 297-305 ◽  
Author(s):  
Yan Ye ◽  
Liang Hui ◽  
Koffi L. Lakpa ◽  
Yuqian Xing ◽  
Hannah Wollenzien ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Silica Nanoparticles ◽  
Hippocampal Neurons ◽  
Calcium Release ◽  
Calcium Stores ◽  
Underlying Mechanisms ◽  
Aβ Generation ◽  
The Brain ◽  
Cultured Hippocampal Neurons

Silica nanoparticles (SiNPs) have been used as vehicles for drug delivery, molecular detection, and cellular manipulations in nanoneuromedicine. SiNPs may cause adverse effects in the brain including neurotoxicity, neuroinflammation, neurodegeneration, and enhancing levels of amyloid beta (Aβ) protein—all pathological hallmarks of Alzheimer’s disease. Therefore, the extent to which SiNPs influence Aβ generation and the underlying mechanisms by which this occurs deserve investigation. Our studies were focused on the effects of SiNPs on endolysosomes which uptake, traffic, and mediate the actions of SiNPs. These organelles are also where amyloidogenesis largely originates. We found that SiNPs, in primary cultured hippocampal neurons, accumulated in endolysosomes and caused a rapid and persistent deacidification of endolysosomes. SiNPs significantly reduced endolysosome calcium stores as indicated by a significant reduction in the ability of the lysosomotropic agent glycyl-l-phenylalanine 2-naphthylamide (GPN) to release calcium from endolysosomes. SiNPs increased Aβ1–40 secretion, whereas 2 agents that acidified endolysosomes, ML-SA1 and CGS21680, blocked SiNP-induced deacidification and increased generation of Aβ1–40. Our findings suggest that SiNP-induced deacidification of and calcium release from endolysosomes might be mechanistically linked to increased amyloidogenesis. The use of SiNPs might not be the best nanomaterial for therapeutic strategies against Alzheimer’s disease and other neurological disorders linked to endolysosome dysfunction.

scholarly journals Toxoplasma gondii injected neurons localize to the cortex and striatum and have altered firing

2021 ◽  
Author(s):  
Oscar A. Mendez ◽  
Emiliano Flores Machado ◽  
Jing Lu ◽  
Anita A. Koshy
Keyword(s):  
Toxoplasma Gondii ◽  
Single Neuron ◽  
Latent Infection ◽  
Ex Vivo ◽  
Medium Spiny Neurons ◽  
Patch Clamping ◽  
Spiny Neurons ◽  
The Brain ◽  
Mapping Program

AbstractToxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. Using immunofluorescence co-localization assays, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2+) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2+). As MSNs have highly characterized electrophysiology, we used ex vivo slices from infected mice to perform single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs (bystander MSNs). These studies demonstrated that TINs have highly abnormal electrophysiology, while the electrophysiology of bystander MSNs was akin to that of MSNs from uninfected mice. Collectively, these data offer new neuroanatomic and electrophysiologic insights into CNS toxoplasmosis.

scholarly journals Short-term and long-term international scientific mobility of Italian PhDs: An analysis by gender

2021 ◽  
pp. 35-40
Author(s):  
Valentina Tocchioni ◽  
Alessandra Petrucci ◽  
Alessandra Minello
Keyword(s):  
Multinomial Logistic Regression ◽  
Early Career ◽  
International Mobility ◽  
Short Term ◽  
Host Countries ◽  
Academic Mobility ◽  
Positive Effects ◽  
Long Run ◽  
The Brain

In the last years, there has been a large increase in high-educated and high-skilled people’s mobility as a consequence of the internationalization and globalization, the weakening of research and university systems of sending countries (the “brain drain” process), the increase in skilled demand and improvements in higher education of host countries (the “brain gain” process). At the micro-level, academic mobility has positive consequences on occupational prospects and careers of researchers, both in the short- and long- run. Nevertheless, numerous research studies have demonstrated the challenges of engaging in international academic mobility for people with caring responsibilities, particularly women. Using Italian data on occupational conditions of PhDs collected in 2018 by Istat and modelling multinomial logistic regression analyses, we intend to verify if female researchers are associated with a lower international mobility irrespective their field of study, and the extent to which gender interacts differently in the various fields of study in affecting the probability of moving abroad after PhD qualification. Also, the distinction between long-term and short-term mobility, which has been mainly neglected in the literature concentrating on longer stays, has taken into account. In this respect, short-term mobility is a potentially high-value investment that may be pursued also by those researchers and scientists who cannot move for longer periods, such as women with caring responsibilities. In the literature, it is acknowledged that an experience abroad during early career may have positive effects on future occupational prospects. With our work, we intend to shed light on potential disparities on moving abroad that may exist among researchers in their early career by gender, and which could contribute to leave behind women in academia.

scholarly journals Functional Connectivity within Brain Networks of Long Term and Short term Meditators

2019 ◽  
Vol 9 (2S) ◽  
pp. 29-34
Keyword(s):  
Functional Connectivity ◽  
Temporal Correlation ◽  
Brain Regions ◽  
Invasive Technique ◽  
Long Term Effects ◽  
Short Term ◽  
Statistical Concept ◽  
The Brain ◽  
Meditative Practices

Meditation refers to a state of mind of relaxation and concentration, where generally the mind and body is at rest. The process of meditation reflects the state of the brain which is distinct from sleep or typical wakeful states of consciousness. Meditative practices usually involve regulation of emotions and monitoring of attention. Over the past decade there has been a tremendous increase in an interest to study the neural mechanisms involved in meditative practices. It could also be beneficial to explore if the effect of meditation is altered by the number of years of meditation practice. Functional Magnetic Resonance Imaging (fMRI) is a very useful imaging technique which can be used to perform this analysis due to its inherent benefits, mainly it being a non-invasive technique. Functional activation and connectivity analysis can be performed on the fMRI data to find the active regions and the connectivity in the brain regions. Functional connectivity is defined as a simple temporal correlation between anatomically separate, active neural regions. Functional connectivity gives the statistical dependencies between regional time series. It is a statistical concept and is quantified using metrics like Correlation. In this study, a comparison is made between functional connectivity in the brain regions of long term meditation practitioners (LTP) and short-term meditation practitioners (STP) to see the differences and similarities in the connectivity patterns. From the analysis, it is evident that in fact there is a difference in connectivity between long term and short term practitioners and hence continuous practice of meditation can have long term effects.

Prolonged retention of the anorectic cobalt protoporphyrin in the hypothalamus and the resulting expression of Fos

2004 ◽  
Vol 287 (2) ◽  
pp. R465-R471 ◽  
Author(s):  
Richard A. Galbraith ◽  
Ilean Hodgdon ◽  
Michele S. Grimm ◽  
Margaret A. Vizzard
Keyword(s):  
Male Rats ◽  
Halothane Anesthesia ◽  
Short Term ◽  
Brain Areas ◽  
Duration Of Action ◽  
Prolonged Duration ◽  
Cobalt Protoporphyrin ◽  
Prolonged Retention ◽  
The Brain

The anorectic cobalt protoporphyrin (CoPP) is known to elicit short-term hypophagia and long-term weight loss through unknown mechanisms in the brains of experimental animals. The goal of this work was to determine 1) if the prolonged duration of action of CoPP is related to its prolonged retention within the brain; and 2) with the use of immunohistochemical detection of Fos, the product of the early-immediate gene c-fos, which cells are activated after exposure to CoPP. These studies were carried out in male rats after intracerebroventricular administration of CoPP, 0.4 μmol/kg body wt, given under light halothane anesthesia. Residence of CoPP in the brain was determined by residual counts in dissected brains of 57CoPP-injected rats. Fos immunoreactivity was mapped in coronal sections of rat brains 4–6 h after injection with CoPP. The results showed that 57CoPP was retained in the hypothalamus preferentially compared with the cortex of the brain and could be detected in the hypothalamus for in excess of 5 wk. Fos activation was increased by CoPP, detected predominantly in neuronal rather than glial cells, and was markedly more robust in the hypothalamus than in other brain areas. Thus CoPP remains in the hypothalamus for prolonged periods and activates Fos expression in the hypothalamus.

Long-term depression of Aplysia sensorimotor synapses in cell culture: inductive role of a rise in postsynaptic calcium

1996 ◽  
Vol 76 (3) ◽  
pp. 2111-2114 ◽  
Author(s):  
X. Y. Lin ◽  
D. L. Glanzman
Keyword(s):  
Cell Culture ◽  
Synaptic Plasticity ◽  
Sensory Neurons ◽  
Tetraacetic Acid ◽  
Short Term ◽  
Long Term Depression ◽  
Central Synapses ◽  
Postsynaptic Calcium

1. Activation of sensory neurons at 2 Hz for 15 min induces long-term depression (LTD) of isolated Aplysia sensorimotor synapses in cell culture. 2. Prior infusion of the Ca2+ chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) into the postsynaptic motor neuron blocks the induction of LTD, but not short-term synaptic depression. 3. Invertebrate central synapses possess the capacity for LTD. This form of long-term synaptic plasticity may play an important role in learning in Aplysia.

Sign in / Sign up

Export Citation Format

Share Document