Search results for " Plasticity"
showing 10 items of 494 documents
Intrinsic volatility of synaptic connections — a challenge to the synaptic trace theory of memory
2017
According to the synaptic trace theory of memory, activity-induced changes in the pattern of synaptic connections underlie the storage of information for long periods. In this framework, the stability of memory critically depends on the stability of the underlying synaptic connections. Surprisingly however, synaptic connections in the living brain are highly volatile, which poses a fundamental challenge to the synaptic trace theory. Here we review recent experimental evidence that link the initial formation of a memory with changes in the pattern of connectivity, but also evidence that synaptic connections are considerably volatile even in the absence of learning. Then we consider different…
Tuning neural circuits by turning the interneuron knob
2017
Interneurons play a critical role in sculpting neuronal circuit activity and their dysfunction can result in neurological and neuropsychiatric disorders. To temporally structure and balance neuronal activity in the adult brain interneurons display a remarkable degree of subclass-specific plasticity, of which the underlying molecular mechanisms have recently begun to be elucidated. Grafting new interneurons to pre-existing neuronal networks allows for amelioration of circuit dysfunction in rodent models of neurological disease and can reopen critical windows for circuit plasticity. The crucial contribution of specific classes of interneurons to circuit homeostasis and plasticity in health an…
Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication.
2020
Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous. For example, presynaptic voltage-gated calcium channels (VGCCs) and postsynaptic ligand-gated ion channels such as AMPA receptors (AMPARs) are organized into so-called nanodomains where individual molecules are only transiently trapped. These pre- and postsynaptic nanodomains are characterized by a high density of molecules but differ in their molecular organization an…
Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System.
2019
Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. The nucleus accumbens (NAc) shell, which integrates the aversive and rewarding valence of stimuli, exhibits plastic adaptations in the presence of pain. In discrete regions of the NAc, activation of the kappa opioid receptor (KOR) decreases the reinforcing properties of rewards and induces aversive behaviors. Using complementary techniques, we report that in vivo recruitment …
Acute Cortical Transhemispheric Diaschisis after Unilateral Traumatic Brain Injury
2017
Focal neocortical brain injuries lead to functional alterations, which can spread beyond lesion-neighboring brain areas. The undamaged hemisphere and its associated disturbances after a unilateral lesion, so-called transhemispheric diaschisis, have been progressively disclosed over the last decades; they are strongly involved in the pathophysiology and, potentially, recovery of brain injuries. Understanding the temporal dynamics of these transhemispheric functional changes is crucial to decipher the role of the undamaged cortex in the processes of functional reorganization at different stages post-lesion. In this regard, little is known about the acute-subacute processes after 24-48 h in th…
Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model
2020
Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms. Recently, auranofin, an anti-inflammatory drug, was shown to have therapeutic potential in a number of diseases in addition to rheumatoid arthritis. Surprisingly, no data regarding the effects of auranofin on cognitive deficits in AD mice or the influence of auranofin on Aβ pathology and n…
Cocaine-induced changes in CX3CL1 and inflammatory signaling pathways in the hippocampus: Association with IL1β
2020
Cocaine induces neuroinflammatory response and interleukin-1 beta (IL1β) is suggested a final effector for many cocaine-induced inflammatory signals. Recently, the chemokine fractalkine (CX3CL1) has been reported to regulate hippocampus-dependent neuroinflammation and synaptic plasticity via CX3C-receptor 1 (CX3CR1), but little is known about the impact of cocaine. This study is mainly focused on the characterization of CX3CL1, IL1β and relevant inflammatory signal transduction pathways in the hippocampus in acute and repeated cocaine-treated male mice. Complementarily, the rewarding properties of cocaine were also assessed in Cx3cr1-knockout (KO) mice using a conditioned place preference (…
Modulation of information processing by AMPA receptor auxiliary subunits
2020
AMPA-type glutamate receptors (AMPARs) are key molecules of neuronal communication in our brain. The discovery of AMPAR auxiliary subunits, such as proteins of the TARP, CKAMP and CNIH families, fundamentally changed our understanding of how AMPAR function is regulated. Auxiliary subunits control almost all aspects of AMPAR function in the brain. They influence AMPAR assembly, composition, structure, trafficking, subcellular localization and gating. This influence has important implications for synapse function. In the present review, we first discuss how auxiliary subunits affect the strength of synapses by modulating number and localization of AMPARs in synapses as well as their glutamate…
Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering m…
2017
Background Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. Methods By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral …
Life history adjustments to intestinal inflammation in a gut nematode.
2017
ABSTRACT Many parasitic nematodes establish chronic infections. This implies a finely tuned interaction with the host immune response in order to avoid infection clearance. Although a number of immune interference mechanisms have been described in nematodes, how parasites adapt to the immune environment provided by their hosts remains largely unexplored. Here, we used the gastrointestinal nematode Heligmosomoides polygyrus to investigate the plasticity of life history traits and immunomodulatory mechanisms in response to intestinal inflammation. We adopted an experimental model of induced colitis and exposed worms to intestinal inflammation at two different developmental stages (larvae and …