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FASEB Journal : Official Publication of... May 2023Associative learning and memory are fundamental behavioral processes through which organisms adapt to complex environments. Associative memory involves long-lasting... (Review)
Review
Associative learning and memory are fundamental behavioral processes through which organisms adapt to complex environments. Associative memory involves long-lasting changes in synaptic plasticity. Dendritic spines are tiny protrusions from the dendritic shaft of principal neurons, providing the structural basis for synaptic plasticity and brain networks in response to external stimuli. Mounting evidence indicates that dendritic spine dynamics are crucial in different associative memory phases, including acquisition, consolidation, and reconsolidation. Causally bridging dendritic spine dynamics and associative memory is still limited by the suitable tools to measure and control spine dynamics in vivo under behaviorally relevant conditions. Here, we review data providing evidence for the remodeling of dendritic spines during associative memory processing and outline open questions.
Topics: Dendritic Spines; Neuronal Plasticity; Brain; Memory; Neurons; Synapses
PubMed: 37000506
DOI: 10.1096/fj.202202166R -
The Neuroscientist : a Review Journal... Feb 2019Dynamic modification of synaptic connectivity in response to sensory experience is a vital step in the refinement of brain circuits as they are established during... (Review)
Review
Dynamic modification of synaptic connectivity in response to sensory experience is a vital step in the refinement of brain circuits as they are established during development and modified during learning. In addition to the well-established role for new spine growth and stabilization in the experience-dependent plasticity of neural circuits, dendritic spine elimination has been linked to improvements in learning, and dysregulation of spine elimination has been associated with intellectual disability and behavioral impairment. Proper brain function requires a tightly regulated balance between spine formation and spine elimination. Although most studies have focused on the mechanisms of spine formation, considerable progress has been made recently in delineating the neural activity patterns and downstream molecular mechanisms that drive dendritic spine elimination. Here, we review the current state of knowledge concerning the signaling pathways that drive dendritic spine shrinkage and elimination in the cerebral cortex and we discuss their implication in neuropsychiatric and neurodegenerative disease.
Topics: Animals; Cerebral Cortex; Dendritic Spines; Humans; Learning; Long-Term Synaptic Depression; Mental Disorders; Neurodegenerative Diseases; Neuroglia; Signal Transduction; Synapses
PubMed: 29716431
DOI: 10.1177/1073858418769644 -
Annual Review of Physiology 2009Dendritic spines are the postsynaptic components of most excitatory synapses in the mammalian brain. Spines accumulate rapidly during early postnatal development and... (Review)
Review
Dendritic spines are the postsynaptic components of most excitatory synapses in the mammalian brain. Spines accumulate rapidly during early postnatal development and undergo a substantial loss as animals mature into adulthood. In past decades, studies have revealed that the number and size of dendritic spines are regulated by a variety of gene products and environmental factors, underscoring the dynamic nature of spines and their importance to brain plasticity. Recently, in vivo time-lapse imaging of dendritic spines in the cerebral cortex suggests that, although spines are highly plastic during development, they are remarkably stable in adulthood, and most of them last throughout life. Therefore, dendritic spines may provide a structural basis for lifelong information storage, in addition to their well-established role in brain plasticity. Because dendritic spines are the key elements for information acquisition and retention, understanding how spines are formed and maintained, particularly in the intact brain, will likely provide fundamental insights into how the brain possesses the extraordinary capacity to learn and to remember.
Topics: Animals; Brain Diseases; Dendritic Spines; Disease Models, Animal; Humans; Learning; Memory; Mice; Neuronal Plasticity; Synapses
PubMed: 19575680
DOI: 10.1146/annurev.physiol.010908.163140 -
Cells Sep 2021Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain... (Review)
Review
Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain increases rapidly before and after birth achieving the highest density around 2-8 years. Density decreases during adolescence, reaching a stable level in adulthood. The changes in dendritic spines are considered structural correlates for synaptic plasticity as well as the basis of experience-dependent remodeling of neuronal circuits. Alterations in spine density correspond to aberrant brain function observed in various neurodevelopmental and neuropsychiatric disorders. Dendritic spine initiation affects spine density. In this review, we discuss the importance of spine initiation in brain development, learning, and potential complications resulting from altered spine initiation in neurological diseases. Current literature shows that two Bin Amphiphysin Rvs (BAR) domain-containing proteins, MIM/Mtss1 and SrGAP3, are involved in spine initiation. We review existing literature and open databases to discuss whether other BAR-domain proteins could also take part in spine initiation. Finally, we discuss the potential molecular mechanisms on how BAR-domain proteins could regulate spine initiation.
Topics: Adaptor Proteins, Signal Transducing; Brain; Brain Diseases; Dendritic Spines; Humans; Learning; Nuclear Proteins; Protein Domains; Tumor Suppressor Proteins
PubMed: 34572042
DOI: 10.3390/cells10092392 -
Progress in Neuro-psychopharmacology &... Jun 2018Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the shape and size of... (Review)
Review
Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the shape and size of dendritic spines correlate with the functional changes in excitatory synapses and are heavily dependent on the remodeling of the underlying actin cytoskeleton. Recent evidence implicates synapses at dendritic spines as important substrates of pathogenesis in neuropsychiatric disorders, including autism spectrum disorder (ASD). Although synaptic perturbations are not the only alterations relevant for these diseases, understanding the molecular underpinnings of the spine and synapse pathology may provide insight into their etiologies and could reveal new drug targets. In this review, we will discuss recent findings of defective actin regulation in dendritic spines associated with ASD.
Topics: Actin Cytoskeleton; Animals; Autism Spectrum Disorder; Dendritic Spines; Humans; Synapses
PubMed: 28870634
DOI: 10.1016/j.pnpbp.2017.08.023 -
Neuroscience Letters Aug 2015Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and... (Review)
Review
Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.
Topics: Age Factors; Animals; Brain; Dendritic Spines; Humans; Schizophrenia
PubMed: 25478958
DOI: 10.1016/j.neulet.2014.11.042 -
Biomolecules Nov 2021Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined... (Review)
Review
Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined areas. These membrane lateral heterogeneities range from nanoscopic dimensions, often involving only a few molecular constituents, to micron-sized mesoscopic domains resulting from the coalescence of nanodomains. Short-lived domains lasting for a few milliseconds coexist with more stable platforms lasting from minutes to days. This panoply of lateral domains subserves the great variety of demands of cell physiology, particularly high for those implicated in signaling. The dendritic spine, a subcellular structure of neurons at the receiving (postsynaptic) end of central nervous system excitatory synapses, exploits this compartmentalization principle. In its most frequent adult morphology, the mushroom-shaped spine harbors neurotransmitter receptors, enzymes, and scaffolding proteins tightly packed in a volume of a few femtoliters. In addition to constituting a mesoscopic lateral heterogeneity of the dendritic arborization, the dendritic spine postsynaptic membrane is further compartmentalized into spatially delimited nanodomains that execute separate functions in the synapse. This review discusses the functional relevance of compartmentalization and nanodomain organization in synaptic transmission and plasticity and exemplifies the importance of this parcelization in various neurotransmitter signaling systems operating at dendritic spines, using two fast ligand-gated ionotropic receptors, the nicotinic acetylcholine receptor and the glutamatergic receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic examples.
Topics: Dendritic Spines; Neurons; Synapses; Synaptic Transmission
PubMed: 34827695
DOI: 10.3390/biom11111697 -
Neural Plasticity 2016Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated... (Review)
Review
Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.
Topics: Animals; Brain; Dendritic Spines; Depressive Disorder; Disease Models, Animal; Female; Humans; Male; Mice; Neuronal Plasticity; Rats; Restraint, Physical; Stress, Psychological
PubMed: 26881133
DOI: 10.1155/2016/8056370 -
Progress in Molecular Biology and... 2015The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in... (Review)
Review
The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in nociceptive pathways. The chronicity of neuropathic pain therefore underscores the importance of understanding the contribution of dendritic spines--micron-sized postsynaptic structures that represent modifiable sites of synaptic contact. Historically, dendritic spines have been of great interest to the learning and memory field. More recent evidence points to the exciting implication that abnormal dendritic spine structure following disease or injury may represent a "molecular memory" for maintaining chronic pain. Dendritic spine dysgenesis in dorsal horn neurons contributes to nociceptive hyperexcitability associated with neuropathic pain, as demonstrated in multiple pain models, i.e., spinal cord injury, peripheral nerve injury, diabetic neuropathy, and thermal burn injury. Because of the relationship between dendritic spine structure and neuronal function, a thorough investigation of dendritic spine behavior in the spinal cord is a unique opportunity to better understand the mechanisms of sensory dysfunction after injury or disease. At a conceptual level, a spinal memory mechanism that engages dendritic spine remodeling would also contribute to a broad range of intractable neurological conditions. Molecules involved in regulating dendritic spine plasticity may offer novel targets for the development of effective and durable therapies for neurological disease.
Topics: Animals; Burns; Dendritic Spines; Diabetic Neuropathies; Humans; Neuralgia; Spinal Cord Injuries; Synapses
PubMed: 25744680
DOI: 10.1016/bs.pmbts.2014.12.001 -
Progress in Neuro-psychopharmacology &... Jun 2019Dendritic spines are small, thin, specialized protrusions from neuronal dendrites, primarily localized in the excitatory synapses. Sophisticated imaging techniques... (Review)
Review
Dendritic spines are small, thin, specialized protrusions from neuronal dendrites, primarily localized in the excitatory synapses. Sophisticated imaging techniques revealed that dendritic spines are complex structures consisting of a dense network of cytoskeletal, transmembrane and scaffolding molecules, and numerous surface receptors. Molecular signaling pathways, mainly Rho and Ras family small GTPases pathways that converge on actin cytoskeleton, regulate the spine morphology and dynamics bi-directionally during synaptic activity. During synaptic plasticity the number and shapes of dendritic spines undergo radical reorganizations. Long-term potentiation (LTP) induction promote spine head enlargement and the formation and stabilization of new spines. Long-term depression (LTD) results in their shrinkage and retraction. Reports indicate increased spine density in the pyramidal neurons of autism and Fragile X syndrome patients and reduced density in the temporal gyrus loci of schizophrenic patients. Post-mortem reports of Alzheimer's brains showed reduced spine number in the hippocampus and cortex. This review highlights the spine morphogenesis process, the activity-dependent structural plasticity and mechanisms by which synaptic activity sculpts the dendritic spines, the structural and functional changes in spines during learning and memory using LTP and LTD processes. It also discusses on spine status in neurodegenerative diseases and the impact of nootropics and neuroprotective agents on the functional restoration of dendritic spines.
Topics: Animals; Dendritic Spines; Humans; Nervous System Diseases; Neuronal Plasticity
PubMed: 30654089
DOI: 10.1016/j.pnpbp.2019.01.005