Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 16

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
INTRODUCTION: A noninvasive method of mapping cortical activation in the same animal before and after behavioral training for assessing experience-dependent cortical plasticity is of great value. Previously, we mapped changes in cortical representation of vibrissae involved in behavioral training with 2-deoxyglucose (2-DG). We wanted to replicate the 2-DG results with ISOI. AIM(S): The aim of the experiments was to find a protocol of vibrissae stimulation for the ISOI from the barrel cortex, which could provide constant signal in temporally separated recordings and enable visualization of plastic changes. METHOD(S): Two subsequent ISOI were performed with 6 days interval. Conditioning consisted of 3 daily sessions of 40 trials of manual stimulation of row B vibrissae on one side of the snout coupled with a mild tail shock. 24 hours after the last conditioning session the second ISOI was performed. Two protocols of vibrissae stimulation during ISOI were tested. In the first protocol 5-ms deflections of B1 vibrissa were applied for 1 s with frequency of 5 Hz (this protocol was used in earlier studies of experience-dependent cortical plasticity seen after whisker deprivation). In the second protocol 5-ms deflections of B1 vibrissa were applied for 6 s with frequency of 10 Hz. Additionally, after second ISOI a 2-DG mapping was performed in order to confirm plasticity in the somatosensory cortex. Using 2-DG method a comparison was performed between left (involved during conditioning) and right (not involved) vibrissae representation. RESULTS: The paired ISOI using the first protocol (1 s/5 Hz) of vibrissae stimulation revealed no change of the B1 vibrissa representation after conditioning, a result that is inconsistent with 2-DG maps. ISOI in which the second vibrissae stimulation protocol (6 s/10 Hz) was applied showed expansion of cortical representation of vibrissa stimulated during conditioning. CONCLUSIONS: Different protocols are suitable for different types of experience-dependent cortical plasticity. FINANCIAL SUPPORT: Project supported by National Science Centre, Poland (DEC-2012/05/D/NZ3/00994).
In laboratory animals, exposure to the enriched environment (EE) induces broad range of modifications in nerve cells at both molecular and anatomical levels. EE also improves animal’s cognitive performance in learning and memory tasks. Despite some progress in revealing the effects of EE on synaptic transmission in the hippocampus, scant and inconsistent data are available on the impact of EE on synaptic properties in the neocortex. The aim of the present study was to examine the influence of the EE exposure on neuronal properties in layer IV of the barrel cortex. Twenty five days old mice (bred under standard laboratory conditions) were put for two weeks to the enriched environment (i.e. to bigger cage with playing tools: tunnels, ladders, a running wheel, spatial maze box and with a set of objects of different shape, made from various fabrics). Control mice were housed in standard laboratory cages during the same period of time. Next, we prepared brain slices containing the barrel cortex and performed visually guided whole-cell recordings from excitatory layer IV neurons within barrels B-D. The results were compared between control and EE-exposed animals. We found that EE experience increased the spontaneous firing rate of excitatory layer IV cells. This phenomenon seems to be due to stronger excitatory synaptic input to these neurons, because both frequency and amplitude of spontaneous excitatory postsynaptic currents were bigger after EE exposure, while kinetic properties of spontaneous inhibitory postsynaptic currents as well as intrinsic excitability remained unchanged. Our results indicate that EE selectively enhances excitatory transmission within the cortical representation of whiskers. The research was supported by the Ministry of Science and Higher Education “PolPostDoc” grant PBZ/MNiSW/07/2006/09 to GY.
INTRODUCTION: Among cortical inhibitory cells, activity of somatostatin interneurons (SST INTs) has been recently proposed as a key player in the formation of neuroplastic changes. Sensory deprivation causes changes in inhibitory systems that lead to disinhibition of the spared barrel, allowing for spreading of its functional representation. Because of their unique pattern of connectivity, we hypothesize that layer IV SST INTs strongly modulate disinhibition of the spared barrel, supporting the sensory deprivation‑induced plastic change formation. AIM(S): Using a chemogenetic approach, we aimed to study a direct role of layer IV SST INTs activity in plastic change formation induced by sensory deprivation in mice barrel cortex. METHOD(S): SST-Cre mice were unilaterally injected with Cre-dependent AAV2 vectors expressing inhibitory DREADDs into a single barrel of row C. Two weeks later, mice underwent a sensory deprivation paradigm, in which all whiskers but one, C3, on one side of the snout were plucked for a week. During deprivation, the activity of SST INTs was blocked by DREADDs activation with its agonist, CNO, continuously administered via Alzet® Osmotic Pumps. To visualize plastic change, [14C]‑2‑deoxyglucose brain mapping was performed. The area of functional representation of the spared whisker and contralateral one was compared. RESULTS: We found that SST INTs inhibition in the spared barrel did not influence the area of activation of the spared whisker compared to transduced animals with saline administration instead of CNO. However, SST INTs blockade in the deprived barrel, adjacent to the spared one, led to a dramatic decrease in functional plasticity of spared whisker representation. CONCLUSIONS: Our results indicate that layer IV SST INTs activity in deprived, but not spared barrel, is essential in sensory deprivation-induced plastic change formation in the barrel cortex of mice. FINANCIAL SUPPORT: Polish National Science Centre Grant to GD (2017/27/N/NZ4/02639).
Sensory deprivation elicits alterations in the functional organization of the primary somatosensory cortex. It was shown that plucking out all but one row of whiskers in adult mice evokes broadening of the functional representation of the spared row, as measured with radioactive 2-deoxyglucose (2-DG) uptake during passive stimulation of whiskers. We would like to establish whether changes in metabolic activity caused by sensory deprivation are paralleled by changes at genomic levels visualized by immediate early genes immunohistochemistry Exploration of enriched environment is a powerful trigger to induce immediate early genes in the barrel cortex. In this study we show that plasticity of the functional representation of the spared row of whiskers can be estimated by radioactive 2-DG method in animals actively using their whiskers while exploring new environment. Expansion of the spared row representation in the deprived hemisphere reaches 140% of the control (non-deprived) hemisphere after 1 week of deprivation and spreads to whole barrel fi eld after four weeks of deprivation. We also show that induction of some early immediate genes during exploration of new environment is limited to the non-deprived barrels after one day of deprivation. In further course of studies we will perform immunohistochemical reactions for proteins encoded by early immediate genes in brains from animals deprived for 1 or 4 weeks.
INTRODUCTION: Associative fear learning, in which stimulation of vibrissae is paired with tail shock results in increased functional cortical representation of the row of whiskers activated during the conditioning. Expansion of the functional cortical representation was revealed with 2-deoxyglucose autoradiography. The chemogenetic DREADD technique allows for precise manipulation of the brain circuits and is based on exclusive activation of designer receptors by designer drug – CNO (Clozapine N-oxide). CNO, which is believed to be pharmacologically inert in mice and rats but not in humans, recently was found to produce some behavioural effects in one of the rat’s strain. AIM(S): Taking into account the possible unspecific results in our chemogenetic experiments in mice, we aimed to determine if CNO administered alone can influence the learning-dependent plasticity. METHOD(S): A group of wild type, C57BL/6J mice underwent behavioural training consisting of 3 sessions of conditioning in three consecutive days. 30 minutes before each session mice were injected intraperitoneally with CNO (1 mg/kg). 24 hours after the third session 2-deoxyglucose procedure was performed. Autoradiograms of tangential brain sections containing the barrel field were analyzed and functional representation of the conditioned row of whiskers and contralateral row on the other side of the snout were mapped. RESULTS: Analysis showed the increased representation of the trained row in the fourth layer of barrel cortex in conditioned hemisphere in comparison to control one. Cortical activity was also observed in other structures like secondary somatosensory cortex and auditory cortex, which replicate the pattern of activation observed in previous experiments. CONCLUSIONS: The results suggest that CNO administered alone does not influence the learning‑‑dependent cortical plasticity and can be applied in chemogenetic experiments within this experimental model of learning in mice. FINANCIAL SUPPORT: Authors are supported by the Polish National Science Centre Grant given to Małgorzata Kossut (2015/17/B/NZ4/02016).
INTRODUCTION: Molecular aging, defined as an age‑related transcriptome changes, and biochemical protein-related alterations within synapses weaken the plastic potential of neurons. Previously, we have shown an age-related impairment of learning-related functional plasticity in mouse somatosensory cortex (SI), induced by associative fear learning and visualized with brain mapping using 2-deoxyglucose technique. AIM(S): The aim of the study was to investigate age-related changes in somatostatin-containing GABAergic interneurons, which are involved in learning – related plasticity in mouse SI. METHOD(S): Learning-related plasticity was induced with classical conditioning, where tactile stimulus to large sensory whiskers was coupled to the tail shock. Two groups of mice were used in the experiments: young (3 months old) and aged (1 year old). We have investigated mRNA and protein level of GAD67 (enzyme synthesizing GABA) and SOM (somatostatin) in mouse SI using q-RT-PCR and ELISA, respectively. Using immunofluorescence we compared the number of both types of neurons in SI. RESULTS: Analysis of q-RT-PCR results revealed no change in investigated mRNAs levels between young and aged mice. We also observed an upregulation of GAD67 and GABA levels after training in young but not in aged animals. Immunohistochemistry results showed an increase in the number of GAD67+ cells, however, we did not observe an elevation in the number of SOM+/GAD67+ cells. CONCLUSIONS: Increase in GAD67+ neurons density after sensory training in aged animals without parallel upregulation in GAD67 and GABA levels suggests lower GABA synthesis resulting in reduced effectiveness of aged GABAergic neurons. Lack of increase in SOM+ neurons density after sensory training in aged mice, suggest that upregulation of SOM+ cells is necessary for training induced plasticity. FINANCIAL SUPPORT: Supported by National Science Centre grant 2013/09/B/NZ3/00540.
INTRODUCTION: Inhibitory interneurons undergo age-related alterations that may have tremendous consequences on cellular and network computations and account for cognitive and behavioral deficits. Accordingly, we have shown that mechanisms governing fear learning‑induced plasticity were weakened in aged (1 y.o.) mice somatosensory cortex, hampering manifestation of plastic changes, while in old (2 y.o.) mice the plasticity was absent. AIM(S): To investigate age-related mRNA changes of distinct markers that are characteristic of GABAergic interneurons, define their main subtypes, and correlate potential changes with age‑related plasticity impairments. METHOD(S): Plasticity was induced with a classical conditioning paradigm, in which tactile stimulus to one row of whiskers was paired with a tail electric shock. Three groups of mice were used: young (3 months old), aged (1 y.o.) and old (2 y.o.). Using qRT‑PCR, we investigated mRNA levels of GAD67, GAD65, parvalbumin (PV), somatostatin (SST), calretinin (CR), calbindin (CB), vasoactive intestinal polypeptide (VIP), and Neuropeptide Y (NPY). RESULTS: qRT‑PCR analysis showed changes in mRNA levels, resulting from both aging itself and from plasticity induction. mRNA level of CB decreased in aged and old animals, whereas PV increased in the old group. After plasticity induction, we observed a reduction of NPY in the young group, while aged animals presented a decline of VIP mRNA levels. We observed decrease in CB along with an increase in PV mRNA levels, which may result in calcium homeostasis disruption in neurons and may consequently be involved in the plasticity impairments observed in aged and old animals. CONCLUSIONS: Being a part of the VIP-SST disinhibitory circuit that exist in many cortical areas, VIP mRNA changes may contribute to dysregulation of this important mechanism controlling plasticity. FINANCIAL SUPPORT: National Science Centre grant 2013/09/B/NZ3/00540.
Synaptic plasticity in the nervous system is associated with rapid state-dependent changes that require constant adaptation of the balance between excitation and inhibition. Increasing neuronal activity has been shown to stimulate the inhibitory system to preserve the excitation/inhibition homeostasis. Experimental data suggest an increased inhibitory GABA-ergic neurotransmission in brain structures involved in the learning process. Previously we have shown that classical conditioning involving stimulation of a row of facial vibrissae in adult mice results in an increased density of GABAergic interneurones and increased cortical expression of glutamic acid decarboxylase in granular layer of trained row representation. Also, we have found that parvalbumin containing subpopulation was not involved in the observed changes. From numerous subpopulations of GABAergic neurons, somatostatin (SST) containing cells seem to be likely involved in regulation of activity and plasticity of neuronal networks. To test this hypothesis we have used the sensory training protocol that was based on the classical conditioning where tactile stimulation of one row of sensory whiskers (CS) was paired with a tail shock (UCS). The training was continued for 3 consecutive days and lasted 10 min each day (40 trials). Cells expressing SST were assessed using stereology-based counting in both hemispheres in the barrel cortex. We have shown the substantial (22%) increase of SST-containing cells in the trained row representation. The result suggests that somatostatin is involved in learning induced changes of inhibitory cortical network. Supported by grant No. 2486/B/P01/2010/39 (M.K.) N N301 248639.
Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set‑Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined. The animals were treated with the inhibitor to elicit a compensatory DAT up‑regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra‑dimensional shift stages was higher in DAT+/− mutant mice than in WT mice. GBR 12909‑treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr‑1, egr‑2) immunohistochemistry. Density of egr‑2 labeled cells in the OFC was lower in mutant mice than in wild‑types during reversal learning and the expression of the egr‑1 was lower in mutant mice in the OFC and DMS during reversal and intra‑dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task‑induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.