Introduction: What Are Dendritic Spines?

Dendritic spines are cellular specializations that greatly increase the connectivity of neurons and modulate the "weight" of most postsynaptic excitatory potentials. Spines are found in very diverse animal species providing neural networks with a high integrative and computational possibility and plasticity, enabling the perception of sensorial stimuli and the elaboration of a myriad of behavioral displays, including emotional processing, memory, and learning. Humans have trillions of spines in the cerebral cortex, and these spines in a continuum of shapes and sizes can integrate the features that differ our brain from other species. In this chapter, we describe (1) the discovery of these small neuronal protrusions and the search for the biological meaning of dendritic spines; (2) the heterogeneity of shapes and sizes of spines, whose structure and composition are associated with the fine-tuning of synaptic processing in each nervous area, as well as the findings that support the role of dendritic spines in increasing the wiring of neural circuits and their functions; and (3) within the intraspine microenvironment, the integration and activation of signaling biochemical pathways, the compartmentalization of molecules or their spreading outside the spine, and the biophysical properties that can affect parent dendrites. We also provide (4) examples of plasticity involving dendritic spines and neural circuits relevant to species survival and comment on (5) current research advancements and challenges in this exciting research field.

Glial Cell Modulation of Dendritic Spine Structure and Synaptic Function.

Glia comprise a heterogeneous group of cells involved in the structure and function of the central and peripheral nervous system. Glial cells are found from invertebrates to humans with morphological specializations related to the neural circuits in which they are embedded. Glial cells modulate neuronal functions, brain wiring and myelination, and information processing. For example, astrocytes send processes to the synaptic cleft, actively participate in the metabolism of neurotransmitters, and release gliotransmitters, whose multiple effects depend on the targeting cells. Human astrocytes are larger and more complex than their mice and rats counterparts. Astrocytes and microglia participate in the development and plasticity of neural circuits by modulating dendritic spines. Spines enhance neuronal connectivity, integrate most postsynaptic excitatory potentials, and balance the strength of each input. Not all central synapses are engulfed by astrocytic processes. When that relationship occurs, a different pattern for thin and large spines reflects an activity-dependent remodeling of motile astrocytic processes around presynaptic and postsynaptic elements. Microglia are equally relevant for synaptic processing, and both glial cells modulate the switch of neuroendocrine secretion and behavioral display needed for reproduction. In this chapter, we provide an overview of the structure, function, and plasticity of glial cells and relate them to synaptic maturation and modulation, also involving neurotrophic factors. Together, neurons and glia coordinate synaptic transmission in both normal and abnormal conditions. Neglected over decades, this exciting research field can unravel the complexity of species-specific neural cytoarchitecture as well as the dynamic region-specific functional interactions between diverse neurons and glial subtypes.

Identification of neural circuits controlling male sexual behavior and sexual motivation by manganese-enhanced magnetic resonance imaging.

Introduction: Different techniques have been used to identify the brain regions that control sexual motivation and sexual behavior. However, the influence of sexual experience on the activation of these brain regions in the same subject is unknown. Using manganese-enhanced magnetic resonance imaging (MEMRI), we analyzed the activation of brain regions in the sexual incentive motivation (SIM) and the partner preference PP (tests) on weeks 1, 5, and 10 in male rats tested for 10 weeks. AIM. In experiment 1, we analyzed the possible toxic effects of 16 mg/kg of MnCl2 on male sexual behavior, running wheel, and motor execution. In experiment 2, subjects were tested for SIM and PP using MEMRI. Methods: In both experiments, a dose of 16 mg/kg (s.c) of chloride manganese (MnCl2) was administered 24 h before subjects were tested and placed immediately thereafter in a 7-Tesla Bruker scanner. Results: In experiment 1, the dose of 16 mg/kg of MnCl2 did not induce behavioral alterations that could interfere with interpreting the imaging data. In experiment 2, we found a clear preference for the female in both the SIM and PP tests. We found a higher signal intensity in the olfactory bulb (OB) in week 1 of the SIM test compared to the control group. We also found increased signal intensity in the socio-sexual behavior and mesolimbic reward circuits in the SIM test in week 1. In the PP test, we found a higher signal intensity in the ventral tegmental area (VTA) in week 10 compared to the control group. In the same test, we found increased signal intensity in the socio-sexual and mesolimbic reward circuits in week 5 compared to the control group. Cohen's d analysis of the whole brain revealed that as the subjects gained sexual experience we observed a higher brain activation in the OB in the SIM group. The PP group showed higher brain activation in the cortex and subcortical structures as they acquired sexual experience. Discussion: As the subjects gain sexual experience, more structures of the reward and socio-sexual circuits are recruited, resulting in different, and large brain activations.

Bridging physiological and perceptual views of autism by means of sampling-based Bayesian inference.

Theories for autism spectrum disorder (ASD) have been formulated at different levels, ranging from physiological observations to perceptual and behavioral descriptions. Understanding the physiological underpinnings of perceptual traits in ASD remains a significant challenge in the field. Here we show how a recurrent neural circuit model that was optimized to perform sampling-based inference and displays characteristic features of cortical dynamics can help bridge this gap. The model was able to establish a mechanistic link between two descriptive levels for ASD: a physiological level, in terms of inhibitory dysfunction, neural variability, and oscillations, and a perceptual level, in terms of hypopriors in Bayesian computations. We took two parallel paths-inducing hypopriors in the probabilistic model, and an inhibitory dysfunction in the network model-which lead to consistent results in terms of the represented posteriors, providing support for the view that both descriptions might constitute two sides of the same coin.

Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats.

During puberty, sexual hormones induce crucial changes in neural circuit organization, leading to significant sexual dimorphism in adult behaviours. The ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) is the major neural site controlling the receptive component of female sexual behaviour, which is dependent on ovarian hormones. The inputs to the VMHvl, originating from the medial nucleus of the amygdala (MeA), transmit essential information to trigger such behaviour. In this study, we investigated the projection pattern of the MeA to the VMHvl in ovariectomized rats at early puberty. Six-week-old Sprague-Dawley rats were ovariectomized (OVX) and, upon reaching 90 days of age, were subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MeA. Projections from the MeA to the VMHvl and to other structures included in the neural circuit responsible for female sexual behaviour were analysed in the Control and OVX groups. The results of the semi-quantitative analysis showed that peripubertal ovariectomy reduced the density of intra-amygdalar fibres. The stereological estimates, however, failed to find changes in the organization of the terminal fields of nerve fibres from the MeA to the VMHvl in the adult. The present data show that ovariectomized rats during the peripubertal phase did not undergo significant changes in MeA fibres reaching the VMHvl; however, they suggest a possible effect of ovariectomy on MeA connectivity under amygdalar subnuclei.

Mouse corticospinal system comprises different functional neuronal ensembles depending on their hodology.

BACKGROUND: Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers. RESULTS: Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups. CONCLUSIONS: The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.

Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1 CreERT2 and Glast CreERT2 Murine Lines.

Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs. In this work, we used genetically modified mice to allow conditional expression of tdTomato (Tom) in adult-born GCs and characterized their development and functional integration. Ascl1(CreERT2);CAG(floxStopTom) and Glast(CreERT2);CAG(floxStopTom) mice resulted in indelible expression of Tom in adult neural stem cells and their lineage upon tamoxifen induction. Whole-cell recordings were performed to measure intrinsic excitability, firing behavior, and afferent excitatory connectivity. Developing GCs were also staged by the expression of early and late neuronal markers. The slow development of adult-born GCs characterized here is consistent with previous reports using retroviral approaches that have revealed that a mature phenotype is typically achieved after 6-8 weeks. Our findings demonstrate that Ascl1(CreERT2) and Glast(CreERT2) mouse lines enable simple and reliable labeling of adult-born GC lineages within restricted time windows. Therefore, these mice greatly facilitate tagging new neurons and manipulating their activity, required for understanding adult neurogenesis in the context of network remodeling, learning, and behavior. SIGNIFICANCE STATEMENT: Our study shows that Ascl1(CreERT2) and Glast(CreERT2) mice lines can be used to label large cohorts of adult-born dentate granule cells with excellent time resolution. Neurons labeled in this manner display developmental and functional profiles that are in full agreement with previous findings using thymidine analogs and retroviral labeling, thus providing an alternative approach to tackle fundamental questions on circuit remodeling. Because of the massive neuronal targeting and the simplicity of this method, genetic labeling will contribute to expand research on adult neurogenesis.