The precise patterns of neuronal assembly during development determine all functional outputs of a nervous system; these may range from simple reflexes to learning, memory, cognition, etc. To understand how brain functions and how best to repair it after injury, disease, or trauma, it is imperative that we first seek to define fundamental steps mediating this neuronal assembly. To acquire the sophisticated ensemble of highly specialized networks seen in a mature brain, all proliferated and migrated neurons must extend their axonal and dendritic processes toward targets, which are often located at some distance. Upon contact with potential partners, neurons must undergo dramatic structural changes to become either a pre- or a postsynaptic neuron. This connectivity is cemented through specialized structures termed synapses. Both structurally and functionally, the newly formed synapses are, however, not static as they undergo consistent changes in order for an animal to meet its behavioral needs in a changing environment. These changes may be either in the form of new synapses or an enhancement of their synaptic efficacy, referred to as synaptic plasticity. Thus, synapse formation is not restricted to neurodevelopment; it is a process that remains active throughout life. As the brain ages, either the lack of neuronal activity or cell death render synapses dysfunctional, thus giving rise to neurodegenerative disorders. This review seeks to highlight salient steps that are involved in a neuron’s journey, starting with the establishment, maturation, and consolidation of synapses; we particularly focus on identifying key players involved in the synaptogenic program. We hope that this endeavor will not only help the beginners in this field to understand how brain networks are assembled in the first place but also shed light on various neurodevelopmental, neurological, neurodegenerative, and neuropsychiatric disorders that involve synaptic inactivity or dysfunction.

Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.

Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid) on cultured, rat cortical neurons.

Neurotrophic factors have well established roles in neuronal development, although their precise involvement in synapse formation and plasticity is yet to be fully determined. Using soma–soma synapses between identified Lymnaea neurons, we have shown recently that trophic factors are required for excitatory but not inhibitory synapse formation. However, neither the precise site (presynaptic versus postsynaptic cell) nor the underlying mechanisms have yet been defined. In the present study, synapse formation between the presynaptic cell visceral dorsal 4 (VD4) and its postsynaptic partner right pedal dorsal 1 (RPeD1) was examined to define the cellular mechanisms mediating trophic factor-induced excitatory synaptogenesis in cell culture. When paired in a soma–soma configuration in the presence of defined media (DM, nonproteinacious), mutually inhibitory synapses were appropriately reconstructed between VD4 and RPeD1. However, when cells were paired in the presence of increasing concentrations of Lymnaea brain-conditioned medium (CM), a biphasic synapse (initial excitatory synaptic component followed by inhibition) developed. The CM-induced excitatory synapse formation required trophic factor-mediated activation of receptor tyrosine kinases in the postsynaptic cell, RPeD1, and a concomitant modulation of existing postsynaptic nicotinic acetylcholine receptors (nAChRs). Specifically, when RPeD1 was isolated in DM, exogenously applied ACh induced a hyperpolarizing response that was sensitive to the AChR antagonist methyllycaconitine (MLA). In contrast, a single RPeD1 isolated in CM exhibited a biphasic response to exogenously applied ACh. The initial depolarizing phase of the biphasic response was sensitive to both mecamylamine and hexamethonium chloride, whereas the hyperpolarizing phase was blocked by MLA. In soma–soma-paired neurons, the VD4-induced synaptic responses in RPeD1 were sensitive to the cholinergic antagonists in a concentration range similar to that used to block cholinergic responses in single RPeD1 cells. Therefore, the modulation of postsynaptic nAChRs was sufficient to account for the trophic factor-induced excitatory synaptogenesis. This study thus provides the first direct evidence that trophic factors act postsynaptically to promote excitatory synapse formation.

Concerns have risen regarding the potential side effects of clinical exposure of the pediatric population to inhalational anesthetics, and how they might impact cognitive, learning, and memory functions. However, neither the mechanisms of anesthetic cytotoxicity, nor potential protective strategies, have yet been fully explored. In this study, we examined whether two of the most commonly used inhalational anesthetics, sevoflurane and desflurane, affect neuronal viability and synaptic network assembly between cultured rat cortical neurons. Primary rat cortical neuron cultures were exposed to equipotent sevoflurane or desflurane for 1 hour. Neuron viability, synaptic protein expression, mitochondrial morphology, and neurite growth were assayed with immunostaining and confocal microscopy techniques. The effects of anesthetics on the functional development of neural networks were evaluated with whole-cell patch clamp recordings of spontaneous synaptic currents. Our results demonstrate that an acute exposure to sevoflurane and desflurane inhibits the development of neurite processes, impacts the mitochondria, and compromises synaptic proteins - concomitant with a reduction in synaptic function in mature networks. Interestingly, pretreatment of neurons with a mitochondrial division inhibitor (Mdivi-1) not only protected mitochondria integrity but also played a protective role against anesthetic-induced structural and functional neurotoxicity. We show that Mdivi-1 likely plays a protective role against certain harmful effects of general anesthetics on primary rat neuronal cultures. In addition, Mdivi-1 alone plays a direct role in enhancing growth and modulating synaptic activity. This study highlights the importance of further study into possible protective agents against anesthetic neurotoxicity.