Topology of synaptic connectivity constrains neuronal stimulus representation, predicting two complementary coding strategies

In motor-related brain regions, movement intention has been successfully decoded from in-vivo spike train by isolating a lower-dimension manifold that the high-dimensional spiking activity is constrained to. The mechanism enforcing this constraint remains unclear, although it has been hypothesized to be implemented by the connectivity of the sampled neurons. We test this idea and explore the interactions between local synaptic connectivity and its ability to encode information in a lower dimensional manifold through simulations of a detailed microcircuit model with realistic sources of noise. We confirm that even in isolation such a model can encode the identity of different stimuli in a lower-dimensional space. We then demonstrate that the reliability of the encoding depends on the connectivity between the sampled neurons by specifically sampling populations whose connectivity maximizes certain topological metrics. Finally, we developed an alternative method for determining stimulus identity from the activity of neurons by combining their spike trains with their recurrent connectivity. We found that this method performs better for sampled groups of neurons that perform worse under the classical approach, predicting the possibility of two separate encoding strategies in a single microcircuit.

Alterations in Excitatory and Inhibitory Synaptic Development Within the Mesolimbic Dopamine Pathway in a Mouse Model of Prenatal Drug Exposure

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca+2 channel subunit α2δ-1, known to be involved in key developmental synaptogenic pathways, in mediating these effects. Pregnant mouse dams were treated orally with either the opioid drug buprenorphine (commonly used in medication-assisted treatment for substance use patients), gabapentin (neuropathic pain drug that binds to α2δ-1 and has been increasingly co-abused with opioids), a combination of both drugs, or vehicle daily from gestational day 6 until postnatal day 11. Confocal fluorescence immunohistochemistry (IHC) imaging of the brains of the resulting wild-type (WT) pups at postnatal day 21 revealed a number of significant alterations in excitatory and inhibitory synaptic populations within the anterior cingulate cortex (ACC), nucleus accumbens (NAC), and medial prefrontal cortex (PFC), particularly in the buprenorphine or combinatorial buprenorphine/gabapentin groups. Furthermore, we observed several drug- and region-specific differences in synaptic connectivity between WT and α2δ-1 haploinsufficient mice, indicating that critical α2δ-1-associated synaptogenic pathways are disrupted with early life drug exposure.

Drosophila gustatory projections are segregated by taste modality and connectivity

Gustatory sensory neurons detect caloric and harmful compounds in potential food and convey this information to the brain to inform feeding decisions. To examine the signals that gustatory neurons transmit and receive, we reconstructed gustatory axons and their synaptic sites in the adult Drosophila melanogaster brain, utilizing a whole-brain electron microscopy volume. We reconstructed 87 gustatory projections from the proboscis labellum in the right hemisphere and 57 in the left, representing the majority of labellar gustatory axons. Morphology- and connectivity-based clustering revealed six distinct clusters, likely representing neurons recognizing different taste modalities. Gustatory neurons contain a nearly equal number of interspersed pre-and post-synaptic sites, with extensive synaptic connectivity among gustatory axons. The vast majority of synaptic connections are between morphologically similar neurons, although connections also exist between distinct neuronal subpopulations. This study resolves the anatomy of labellar gustatory projections, reveals that gustatory projections are likely segregated based on taste modality, and uncovers synaptic connections that may alter the transmission of gustatory signals.

Applied neuroscience in early childhood and high school education

Neuroeducation is a very complex practice that has allowed us to know how the human brain acts from its plasticity and wide synaptic connectivity, one of its important characteristics is that it acts cognitively and emotionally, strengthening the teaching-learning process from an early age. An analysis is made of the ideas that various authors have had in the application of neurosciences in the educational field. The objective of this work was to identify, through the interpretation of data, what was the contribution of neurosciences in children in initial and preparatory education of the Mathius Quintanilla Sierra Educational Unit, in the city of Portoviejo, as well as the methods, techniques and strategies used by teachers for the construction of knowledge. The methodology used was non-experimental, descriptive and explanatory, from which it was possible to analyze and understand the information raised by various authors from their professional and personal perspective.

Beneficial Effects of a Plasma Fraction on Inflammation and Synaptic Deficits for Age-Related Cognitive Disorders

The process of aging is multifactorial, and therefore single agent interventions would be unlikely to attenuate the myriad pathologies associated with advancing age. Plasma contains many beneficial factors which have been shown in animal models to ameliorate multiple age-related deficits across varied organ systems, including the brain. We confirmed that human plasma from young (18-22-year-old) donors reverses age-related cognitive decline and enhances hippocampal neurogenesis and cell survival in aged immunocompromised mice, while plasma from aged individuals (62-68 years old) has detrimental effects in young mice. We examined PF in a high-fat diet (HFD) mouse model, a surrogate for a western diet, which expresses many characteristics of aging within the CNS in an accelerated manner: decreased cell proliferation, synaptic connectivity and increased inflammation compared to normal diet (NC) controls. We demonstrate that PF administration in HFD mice resulted in decreased brain inflammation, increased synaptic connectivity, improved neural progenitor cell survival, as well as amelioration of behavioral endpoints without impacting the underlying metabolic changes induced by HFD. In summary, we demonstrate that PF is a multifactorial and multimodal intervention for the treatment of global changes induced by the process of aging.

Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans

Sexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons. In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.

Enhanced synchronization between prelimbic and infralimbic cortices during fear extinction learning

The ability to extinguish aversive memories when they are no longer associated with danger is critical for balancing survival with competing adaptive demands. Previous studies demonstrated that the infralimbic cortex (IL) is essential for extinction of learned fear, while neural activity in the prelimbic cortex (PL) facilitates fear responding and is negatively correlated with the strength of extinction memories. Though these adjacent regions in the prefrontal cortex maintain mutual synaptic connectivity, it has been unclear whether PL and IL interact functionally with each other during fear extinction learning. Here we addressed this question by recording local field potentials (LFPs) simultaneously from PL and IL of awake behaving rats during extinction of auditory fear memories. We found that LFP power in the fast gamma frequency (100–200 Hz) in both PL and IL regions increased during extinction learning. In addition, coherency analysis showed that synchronization between PL and IL in the fast gamma frequency was enhanced over the course of extinction. These findings support the hypothesis that interregional interactions between PL and IL increase as animals extinguish aversive memories.

Quantitative Study of Alpha-Synuclein Prion-Like Spreading in Fully Oriented Reconstructed Neural Networks Reveals Non-synaptic Dissemination of Seeding Aggregates

Background: The trans-neuronal spread of protein aggregation in a prion-like manner underlies the progression of neuronal lesions in the brain of patients with synucleinopathies such as Parkinson’s disease. Despite being studied actively, the mechanisms of alpha-synuclein (aSyn) aggregates propagation remain poorly understood. Indeed, in vivo models of aSyn prion-like propagation yield results whose interpretation is hindered by the complexity of brain networks, and in vitro models have for now failed to properly model trans-neuronal propagation in synaptically connected neural networks.Results: To assess the role of synaptic structures and neuron characteristics in the transfer efficiency of aggregates with seeding propensity, we developed a novel microfluidic neuronal culture system. This system is the first to guide in vitro the development of fully oriented, synaptically connected and fluidically isolated neural networks. It thus uniquely permitted us to model the trans-neuronal propagation of aggregation: we selectively exposed the presynaptic compartment of reconstructed networks to well characterized human aSyn aggregates differing in size (Fibrils and Oligomers), and quantitatively followed their dissemination to postsynaptic neurons. Both aggregates were anterogradely transferred to through active axonal transport, albeit with poor efficiency. By manipulating network maturity, we compared the transfer rate of aggregates in networks with distinct levels of synaptic connectivity. Surprisingly, we found that transfer efficiency was lower in mature networks with higher synaptic connectivity. We then investigated the seeding efficiency of endogenous aSyn in the postsynaptic population. We found that exposure to Fibrils, and not Oligomers, resulted in low efficiency trans-neuronal seeding which was restricted to postsynaptic axons. Finally, we assessed the impact of neuron characteristics and aSyn expression on the propagation of aSyn aggregates, and found that while endogenous aSyn expression level controlled the seeding of aSyn aggregation, it did not affect the transfer rate of exogenous aggregates. Conclusion: Overall, we describe here the first culture system for reconstructing in vitro fully oriented and synaptically connected neural networks, and demonstrate it is uniquely suitable to quantitatively interrogate original aspects of the trans-neuronal propagation of prion-like aggregates.