European Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 57(9), P. 1447 - 1465

Published: March 15, 2023

The brain is a complex assembly of interconnected neurons where synapses enable the transmission information. Synapses are progressively established in via mechanisms neuronal competition, that fire together, wire together (Hebb, 1949). In other words, most efficient strengthened and maintained throughout life, enabling to have plastic response ever-changing environment. This process, globally known as synaptic plasticity, was thought involve exclusively pre-synaptic post-synaptic neurons, through fine regulation calcium channels neurotransmitter receptors, among others. Indeed, classical view connection an electrical signal leading release from neuron, which then binds on receptors ultimately inducing behavioural response. Obviously, learning memory processes mammalian more elaborate than this simplistic rooted precise molecular cellular players. last couple decades, concept plasticity has been expanded, new evidence uncovered that, besides glial cells also take fundamental role synapse development, homeostasis life. Today, astrocytes, microglia oligodendrocytes their precursors considered essential elements for functions malleability. XIXth century, Spanish neuroanatomist Santiago Ramón y Cajal already suggested may be mediated by strengthening improve efficiency communication. perception modulating connectivity long-term potentiation (LTP), lasting increase strength following high-frequency stimulation (Lømo, 2003); its counterpart depression (LTD). Our increasing understanding shed light crucial activity-dependent active cells, providing holistic conception how functions. miscellaneous fact guided almost infinite possibilities fine-tune efficacy information transmission. Spatial temporal readjustments include affecting different cell types present, stabilization or destabilization processes, binding neurotransmitters modulation signal, Impairments formation, remodelling, pruning underlie neurodevelopmental neurological disorders. A better comprehension these would stepping-stone develop pharmacological treatments pathologies fatal nowadays, including Alzheimer's disease. XIth Conference ‘New Frontiers Neuron-Glial Plasticity Health Disease’, organized Society Neuroscience (SENC), took place Sant Feliu de Guíxols, Spain (18–20 May 2022) (Figure 1), devoted discussing neuronal-glial both physiological pathological conditions. conference occurred open informal atmosphere, lively fruitful discussions between participants, plenary speakers, PhD students early career postdoctoral researchers. Students recorded entertaining video abstracts present latest publications speakers whole attendance enjoyed cultural recreational activities, such visit local History Museum kayaking Mediterranean coast. editorial summarizes main findings discussed at conference. These included insights into mechanisms, with focus involvement protein synthesis potentiation, well ones, highlighting relevance regulating membrane fusion receptors. astrocytic control function matter debate, sculpting remodelling synapses. Finally, impairment neurodegenerative diseases addressed relevant roles proteases, presenilin disintegrin metalloproteinase 10, were discussed. Understanding circuits stabilized time, making some them whereas others weakened, major task neuroscience. process refers modifications regulated several neuron. Synaptic enables mammals adapt lifetime experiences modification occurs two ways: modifying (e.g., opening channels; Scarnati et al., 2020) expression (Woo 2020; Wu 2020). relative importance subject debate years (Padamsey & Emptage, 2013) source thrilling Conference. Pablo E. Castillo (Albert Einstein College Medicine, USA) gave involved LTP. During LTP, cyclicAMP/Protein Kinase signalling cascade activated (Castillo, 2012) 2), membrane, bind taking part well-defined, ones remain unclear (Monday Castillo, 2017), but contribute ways (Mizusaki 2022). One form mature retrograde endocannabinoid (eCB) system (Castillo 2012). provided demonstrating implication cannabinoid-receptor 1 (CB1) mediating LTD inhibitory involves protein-synthesis-dependent long-lasting reduction γ-aminobutyric acid (GABA) (Younts 2016). Arnaldo Parra-Damas Carlos A. Saura's group (Institut Neurociències UAB, Spain). He highlighted activity triggers CREB-regulated transcription coactivator-1 (CRTC1) activity, hippocampus (Parra-Damas 2014; 2017). raised considerations about recurrent circuit hilar mossy (MC), first reported (Kobayashi 1996; Zalutsky Nicoll, 1990), granule (GC). takes dentate gyrus hippocampus, one regions responsible processes. LTP enhances output excitation/inhibition balance (Hashimotodani epilepsy, altered. Thus, hippocampal might stages epileptogenesis contributing seizure generation propagation (Nasrallah exposed excitatory undergo novel pre-synaptic, N-methyl-d-aspartate receptor (NMDAR)-independent, requires brain-derived neurotrophic factor (BDNF)/TrkB cyclic AMP (cAMP)/PKA 2017) 2). cAMP needed axonal arbor co-stabilization, described Alice Louail Amanda Sierra's laboratory (Achucarro Basque Center Neuroscience, She explained subset facilitates elimination projections neighbouring (Louail pre- mentioned earlier, neuron advocated Sandra Jurado (Instituto Neurociencias Alicante, Spain), who dendritic exocytosis underlying plasticity. Membrane require participation soluble N-ethylmaleimide sensitive attachment (SNARE) Sec1/Munc18 (SM)-like proteins, vesicle terminals (Südhof Rizo, 2011). However, little level. measure changes ratio glutamatergic receptors: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) (AMPARs) NMDARs. Because kinetics activation NMDAR Ca2+-dependent (Malenka 1999), AMPA/NMDA ratio, increases decreases LTD, indicative what (Counotte 2014). Jurado's presentation focused machinery mediates AMPARs during SNARE synaptobrevin 2/vesicle-associated 2 (VAMP2) AMPAR constitutive basal exocytosis. syntaxin-3 SNAP-47, only required (Arendt 2015; 2013; Madrigal 2019) supports idea unique SNARE-mediated (Jurado, specific complexes regulate forms context, Rocío Rojas, Núria Casals' (International University Catalonia, trafficking plasma can nutrients saturated unsaturated fatty acids. addition AMPARs, there additional exocytic events dendrites, endogenous neuropeptides, play important emphasized hypothalamic neuropeptides oxytocin vasopressin, neuromodulators whose determines appropriate social behaviour (Rigney 2022; Torres 2018). order developmental dynamics her used immunolabeling-enabled three-dimensional imaging solvent-cleared organs (iDISCO+) clearing technique (Renier 2016) light-sheet ultraresolution obtain 3D reconstructions entire oxytocinergic vasopressinergic systems central nervous (CNS). multidisciplinary approach enabled advances neuromodulatory circuits. Strikingly, she distinct nuclei show strong differences vasopressin depending stage (Madrigal Jurado, 2021). adaptations defining functional properties behaviours. Although day not implicated Some decades ago, it participate process. Glial (astrocytes, microglia, others) represent significant population account least half total volume (Azevedo 2009). second Besides his studies many (Ramón Cajal, 1897) (Navarrete Araque, Yet, revealed century later. At Conference, Alfonso Araque (School Minnesota, launched beautiful summary 1998, work demonstrated astrocytes It had decade express large array neuromodulator glutamate (NMDA, AMPA, kainate, mGluR), GABA, acetylcholine (ACh), dopamine (DA). Many coupled second-messenger induces Ca2+ (Verkhratsky 1998). Under glutamtergic axons, ‘spills over’ activates causing elevation intracellular levels (Porter McCarthy, 1996). Astrocytic culture slices (Bezzi 1998; Kimelberg 1990). (Hassinger 1995; Nedergaard, 1994). All strongly suggest Araque's actually able opposite manners. On hand, they glutamate-dependent depression, reducing amplitude currents (EPSCs) (IPSCs) (Araque, Parpura, frequency, amplitude, EPSC IPSCs Sanzgiri, line previous reports showing neurotransmission wave propagates adjacent (Cornell-Bell activity-induced leads inhibits 1998) 3). observation, combined using reconstruction, envelop cleft (Ventura Harris, led him propose concept, revolutionizing synapses: ‘Tripartite synapse’ (Araque 1999). Since then, tripartite tremendous work. Astrocytes respond distinctly synchronous miniature events, generating either robust regional elevations, producing highly confined, fast responses, respectively (Di Castro discriminate belonging pathways (Perea 2005) patterns frequency input activity. Their range responses varies spatial diffusion When coincides elevation, trigger potentiation. transient depends region-specific metabotropic (mGluR) CA1 region 2012; Navarrete 2010; Perea 2007) (Jourdain 2007). coincidence Ca2+-mediated (LTP) contrast, cortex, released stimulated activating (Min Nevian, potentiate acting kainate CA Other shown induce DA seems modulate concentration directions. D1 D2 mobilizes stores increase, decrease (Jennings (see Figure presented research laboratory. performed done another region, nucleus accumbens. They showed optogenetic axons elevations. elevations provoke ATP/adenosine (Corkrum 2020), suggesting reward system. Endocannabinoids CB1 2010) chronic exposure tetrahydrocannabinol (THC) Cristina Martín-Monteagudo's Marta Navarrete's CSIC, Neuronal cholinergic muscarinic mGluR 2002; investigating global network cortical sensory stimulation, interact negatively low-frequency (0–4 Hz) delta positively sensory-evoked (30–50 gamma (Lines synchronization Claudia Miguel-Quesada's Juliana M. Rosa Juan Aguilar (Hospital Nacional Parapléjicos, Network desynchronization dysfunction common feature number often glia. Álvaro Fernández-Blanco Mara Dierssen's (Center Genomic Regulation, Spain) urged impaired astrocyte communication impairments (Fernández-Blanco Dierssen, How finely wide remains debate. Another type Pío del Río Hortega 1919 (Rio-Hortega, 1919). Traditionally linked inflammatory over 50 uncover physiology (Sierra 2019). Microglia ‘constant gardeners’, continuously scanning parenchyma dynamic (Davalos 2005; Nimmerjahn 2005). Once established, few revealed. years, variety ion channels, connexins, cytokines chemokine neurotransmitters, neurohormone (Kettenmann Similar expressed transients, connectivity. Paolicelli (University Lausanne, Switzerland) comprehensive talk overview monitoring remodelling. developing system, transiently contact phagocytic structures (Ji Tremblay Wake 2015), pointing formation stabilization. Paolicelli's pioneer engulf material necessary development (Paolicelli surveying phagocytosis apoptotic 2010), engulfment phagocytosis, or, recently, ‘trogocytosis’ (Weinhard Beth Stevens demonstration prune manner. engulfed colocalizes lysosomal markers (Schafer As consequence, ‘four-way’ ‘Quad-partite’ emerged Gross, 2011; Schafer 2013). tasks today structural particularly stages, fashion. Several pathways, fractalkine signalling, DAP12/triggering myeloid (TREM2) phosphatidylserine complement pathway, removal (Filipello 2018; Scott-Hewitt Microglia-mediated age-dependent visual peak microglial preferential microglia-mediated coming ‘weaker’ eye Microglial contacts reduced when altered, (Tremblay neurotransmission. Active ATP purinergic P2Y12 extension towards (Eyo Fontainhas 2011) GABA displays effects motility (Fontainhas Fractalkine sense Fractalkine-deficient models defective migration, induction, spontaneous/miniature EPSC, decreased performances, stereotyped defects (Pagani Rogers Zhan Most synapses, positioning parvalbumin interneurons (Thion 2019), development. Very specialized expressing GABAB1 receptor, complement-dependent mechanism (Favuzzi suggests maintenance brain. clear need types; involving reported. modulates spontaneous (Pascual Hippocampal lactate, participates microglia-dependent induction (Zhang, Malik, 2014) Interestingly, lactate (Newman Suzuki laboratory's projects concerning metabolism, acidification (Monsorno Lactate transporters microglia. dehydrogenase B, preferably converts pyruvate, abundant genes (Pinto New regularly identified, fully understood. bidirectional topic compelling participants aspects maturation, previously cerebellar (Ayata Stowell 2018), could population, neural/glial antigen (NG2) proteoglycan, identified end XXth (Stallcup Beasley, 1987). referred precursor (OPCs) (Dawson 2000). morphology resembles motile like gene signature (Haberlandt NG2 (Larson 2016), receive mainly localized modify (Ge 2006), although cannot generate action potentials (De Biase 2010). surface appear soon generated transferred daughter divide, disappear differentiate oligodendrocytes, along drastic change transcriptomic (Kukley 2008; Ge 2009; De Kukley Zhang, Chen, period myelination areas (Mangin Vélez-Fort differentiation therefore playing myelination. oligodendrocyte (Cavaliere Chen GABAergic (Serrano-Regal cannabinoid (Sánchez-de la Torre conference, Staffa Isabel Perez-Otaño's (Neuroscience Institute oligodendrocytes. panel determined. Recently, neural cortex. Young manner (Auguste 2022), similar further expanded extracellular matrix (ECM) (Dityatev Rusakov, Dityatev Schachner, 2003; 2006). (pre- ECM molecules) key thus (Pelucchi third consequences regard, tackled issue angles, perspective, time disease (AD), worldwide. AD, affects estimated million people worldwide, no effective treatment gradually impairs memory. histopathological hallmark AD th

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