Cannabinoids can affect a variety of cognitive and performance tasks, including learning, memory,... more Cannabinoids can affect a variety of cognitive and performance tasks, including learning, memory, and attention (Hampson and Deadwyler, 1999). A well-known cellular effect of cannabinoids is the presynaptic inhibition of both GABAergic and glutamatergic transmission throughout the brain (Hohmann et al., 2005). In the hippocampus, this effect Physiology and Abstract Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short-and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Materials and Methods: Drugs were administered three times daily for seven consecutive days into la...
Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is me... more Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is mediated through their action on gamma-aminobutyric acid type A (GABAA) receptors. On the other hand, cannabinoids can affect learning and memory process through presynaptic modulation of the release of both excitatory glutamate and inhibitory GABA transmitters in brain regions involved in learning and memory. The aim of the present study was to investigate the effect of cannabinoids on memory impairment and long-term potentiation (LTP) reduction properties of the short acting benzodiazepine midazolam. Materials and Methods: One week after insertion of guide cannula by stereotaxic surgery, cannabinoid compounds or midazolam were administered by intracerebroventricular (i.c.v.) injection into lateral ventricle of male rats. Spatial memory task was evaluated using Morris water maze (MWM) test. Electrophysiological evaluation was done by field potential recording of hippocampal neurons in unc...
Optogenetics comprises a growing family of related techniques for the optical interrogation and c... more Optogenetics comprises a growing family of related techniques for the optical interrogation and control of excitable cells. Combining genetic targeting with light delivery systems makes it possible to drive or silence subpopulations of neurons and the related behaviours, with a high spatiotemporal precision. Since optical manipulation is fast, selective, and minimally invasive, it provides distinct advantages over traditional electrical means or pharmacological approaches for cell perturbation. Here we showed in anesthetized rat that optogenetic stimulation of nucleus accumbens (NAc) neurons increased neural activation. We labelled a population of neurons activated with channelrhodopsin-2 (ChR2) and later optically stimulated these neurons by using an optrode and recorded spontaneous action potentials from the one neuron.
In order to use an optogenetic technique for controlling closed-loops of neurological diseases, i... more In order to use an optogenetic technique for controlling closed-loops of neurological diseases, it is necessary to design and fabricate an implantable optrode as an optical and electrical system for simultaneous optical stimulation and electrical recording from neural. Microdrive is electrical and optical system that fix on the rat skull and can be used to record neural activity without disturbing the behavior of the animal. It can also be used optical fiber for optical stimulation simultaneously, so it can be used as optrode in closed-loop control systems for neurological diseases based on optogenetic technique. In this paper, an optrode based on motorized microdrive was designed and fabricated. It was used for in-vivo single unit recording in an anesthetized rat.
Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyr... more Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short- and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Materials and Methods: Drugs were administered three times daily for seven consecutive days into lateral ventricle of rats. Short term synaptic plasticity was assessed by measuring paired - pulse index (PPI) in DG neurons after stimulation of perforant pathway. Long-term plasticity was assessed through measurement of both population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope after high frequency stimulation (HFS) of DG neurons. Results: Repeated administration of WIN55212-2 not only significantly decreased PPI in 20, 30 and 50 ms intervals but also blocked LTP. This effect was reversed by pretreatment of rats with CB1 receptor antagonist AM251. Moreover, AM251 by itself increased PPI in 10 and 20 ms interval stimulations, but had no effect on HFS-induced PS amplitude and fEPSP slope. Conclusion: These results suggest that repeated administration of cannabinoids could impair short term and long term synaptic plasticity that may be due to desensitization of cannabinoid receptors and/or changes in synaptic spine density of hippocampus which leads to alteration in short and long term memories that remains to be elucidated.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2021
Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory.... more Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day) and the expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, is mediated by insulin increase in dentate gyrus and subsequently activation of its downstream signaling pathway.
Cannabinoids can affect a variety of cognitive and performance tasks, including learning, memory,... more Cannabinoids can affect a variety of cognitive and performance tasks, including learning, memory, and attention (Hampson and Deadwyler, 1999). A well-known cellular effect of cannabinoids is the presynaptic inhibition of both GABAergic and glutamatergic transmission throughout the brain (Hohmann et al., 2005). In the hippocampus, this effect Physiology and Abstract Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short-and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Materials and Methods: Drugs were administered three times daily for seven consecutive days into la...
Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is me... more Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is mediated through their action on gamma-aminobutyric acid type A (GABAA) receptors. On the other hand, cannabinoids can affect learning and memory process through presynaptic modulation of the release of both excitatory glutamate and inhibitory GABA transmitters in brain regions involved in learning and memory. The aim of the present study was to investigate the effect of cannabinoids on memory impairment and long-term potentiation (LTP) reduction properties of the short acting benzodiazepine midazolam. Materials and Methods: One week after insertion of guide cannula by stereotaxic surgery, cannabinoid compounds or midazolam were administered by intracerebroventricular (i.c.v.) injection into lateral ventricle of male rats. Spatial memory task was evaluated using Morris water maze (MWM) test. Electrophysiological evaluation was done by field potential recording of hippocampal neurons in unc...
Optogenetics comprises a growing family of related techniques for the optical interrogation and c... more Optogenetics comprises a growing family of related techniques for the optical interrogation and control of excitable cells. Combining genetic targeting with light delivery systems makes it possible to drive or silence subpopulations of neurons and the related behaviours, with a high spatiotemporal precision. Since optical manipulation is fast, selective, and minimally invasive, it provides distinct advantages over traditional electrical means or pharmacological approaches for cell perturbation. Here we showed in anesthetized rat that optogenetic stimulation of nucleus accumbens (NAc) neurons increased neural activation. We labelled a population of neurons activated with channelrhodopsin-2 (ChR2) and later optically stimulated these neurons by using an optrode and recorded spontaneous action potentials from the one neuron.
In order to use an optogenetic technique for controlling closed-loops of neurological diseases, i... more In order to use an optogenetic technique for controlling closed-loops of neurological diseases, it is necessary to design and fabricate an implantable optrode as an optical and electrical system for simultaneous optical stimulation and electrical recording from neural. Microdrive is electrical and optical system that fix on the rat skull and can be used to record neural activity without disturbing the behavior of the animal. It can also be used optical fiber for optical stimulation simultaneously, so it can be used as optrode in closed-loop control systems for neurological diseases based on optogenetic technique. In this paper, an optrode based on motorized microdrive was designed and fabricated. It was used for in-vivo single unit recording in an anesthetized rat.
Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyr... more Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short- and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Materials and Methods: Drugs were administered three times daily for seven consecutive days into lateral ventricle of rats. Short term synaptic plasticity was assessed by measuring paired - pulse index (PPI) in DG neurons after stimulation of perforant pathway. Long-term plasticity was assessed through measurement of both population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope after high frequency stimulation (HFS) of DG neurons. Results: Repeated administration of WIN55212-2 not only significantly decreased PPI in 20, 30 and 50 ms intervals but also blocked LTP. This effect was reversed by pretreatment of rats with CB1 receptor antagonist AM251. Moreover, AM251 by itself increased PPI in 10 and 20 ms interval stimulations, but had no effect on HFS-induced PS amplitude and fEPSP slope. Conclusion: These results suggest that repeated administration of cannabinoids could impair short term and long term synaptic plasticity that may be due to desensitization of cannabinoid receptors and/or changes in synaptic spine density of hippocampus which leads to alteration in short and long term memories that remains to be elucidated.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2021
Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory.... more Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day) and the expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, is mediated by insulin increase in dentate gyrus and subsequently activation of its downstream signaling pathway.
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Papers by Abdolaziz Ronaghi