Refinement of Active and Passive Membrane Properties of Layer V Pyramidal Neurons in Rat Primary Motor Cortex During Postnatal Development

Achieving the distinctive complex behaviors of adult mammals requires the development of a great variety of specialized neural circuits. Although the development of these circuits begins during the embryonic stage, they remain immature at birth, requiring a postnatal maturation process to achieve these complex tasks. Understanding how the neuronal membrane properties and circuits change during development is the first step to understand their transition into efficient ones. Thus, using whole cell patch clamp recordings, we have studied the changes in the electrophysiological properties of layer V pyramidal neurons of the rat primary motor cortex during postnatal development. Among all the parameters studied, only the voltage threshold was established at birth and, although some of the changes occurred mainly during the second postnatal week, other properties such as membrane potential, capacitance, duration of the post-hyperpolarization phase or the maximum firing rate were not defined until the beginning of adulthood. Those modifications lead to a decrease in neuronal excitability and to an increase in the working range in young adult neurons, allowing more sensitive and accurate responses. This maturation process, that involves an increase in neuronal size and changes in ionic conductances, seems to be influenced by the neuronal type and by the task that neurons perform as inferred from the comparison with other pyramidal and motor neuron populations.

Features of the expression of Fox-1 in rat’s thyroid after prenatal dexamethasone action

The purpose of the work was to establish the features of Fox-1 expression and distribution in the parenchyma of the thyroid gland of rats in the postnatal period of ontogeny in the norm and after intrauterine action of dexamethasone.Material and methods: thyroid gland of rats (162 animals) of the Wistar line at the age from 1 to 14 days of postnatal development. Experimentally, the animals were injected intrauterinely with a solution of dexamethasone at a dose of 0.05 ml at a dilution of 1:40 on the 18th day of the dated pregnancy. The material was examined using a set of methods of morphological studies (production of histological serial sections, survey microscopy, morphometry, immunohistochemistry and statistical processing).Results of the research. In the thyroid glands of neonatal prenatal dexamethasone, the parenchyma was well developed and consisted of hollow colloid-type follicles and single colloid-type microfollicles, and a bright cytoplasmic reaction with Fox-1 antibodies was observed throughout the organ parenchyma. In the thyroid glands of animals of the 3rd day of life, morphological changes occurred in all groups of the experiment. In animals of the experimental group, hollow follicles of colloidal type of small, medium and large diameter were chaotically visualized throughout the body, and large follicles of irregular shape with immunohistochemical weak or negative reaction with Fox-1 antibodies in thyrocytes and lumen without colloidal evidence, which detected a decrease in the specific synthetic activity in these thyrocytes. On day 7 in the experimental group in the flattened thyrocytes of overstretched follicles, the expression of Fox-1 was present only in the apical part. On days 11-14 of postnatal development in the thyroid glands of rats experimentally prenatally exposed to dexamethasone in the wall of large follicles with flattened epithelium began extrafollicular proliferation of thyrocytes on the background of visualization in the lumen of these follicles desquamated cells. Intensive perinuclear and cytoplasmic Fox-1 positive reaction was present in extrafollicular proliferating thyrocytes.Conclusions. 1. The detected changes in the first day of life in the thyroid gland of rats indicated that prenatal administration of dexamethasone affects the intensification of differentiation not only structural and functional units - follicles, but also a specific synthetic intracellular apparatus of thyrocytes, judging by the intensification of Fox-1. Thus, immature pre-mRNA is converted into mature mRNA, from which thyroid proteins, in particular thyroglobulin, are translated. By the time of birth, this process in the experimental group reaches a significant development, covering the entire parenchyma of the gland. 2. In rats prenatally receiving dexamethasone, the period of lactation was characterized by intense structural changes in the thyroid gland, in particular intracellularly in thyrocytes of monolayer flattened epithelium, the expression of Fox-1 antibodies was sharply reduced, which was then replaced by a bright cytoplasmic reaction in proliferative clusters and follicles of colloidal type of secretion, which is an adaptive-compensatory mechanism of intracellular enhancement of proliferation of synthesizing organelles in response to the restructuring of a significant number of existing follicles by hypofunctional type, aimed at maintaining normal levels of thyroid function.

The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination

Background Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination. Methods To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo. Results We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood. Conclusions We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.

Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

The size principle underlies the orderly recruitment of motor units; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motoneuron subtypes. Whilst intrinsic properties are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential activation of delayed and immediate firing motoneuron subtypes. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that contribute to rheobase and may be important to establish orderly recruitment. We find that delayed and immediate firing motoneurons are functionally homogeneous during the first postnatal week and are activated based on size, irrespective of subtype. The rheobase of motoneuron subtypes become staggered during the second postnatal week, which coincides with the differential maturation of passive and active properties, particularly persistent inward currents. Rheobase of delayed firing motoneurons increases further in the third postnatal week due to the development of a prominent resting hyperpolarization-activated inward current. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.

Postnatal development of centrifugal inputs to the olfactory bulb

Processing in primary sensory areas is influenced by centrifugal inputs from higher brain areas, providing information about behavioral state, attention, or context. Activity in the olfactory bulb, the first central processing stage of olfactory information, is dynamically modulated by direct projections from a variety of areas in adult mice. Despite the early onset of olfactory sensation compared to other senses, the development of centrifugal inputs to the olfactory bulb remains largely unknown. Using retrograde tracing across development, we show that centrifugal projections to the olfactory bulb are established during the postnatal period in an area-specific manner. While feedback projections from the piriform cortex are already present shortly after birth, they strongly increase in number during postnatal development with an anterior-posterior gradient. Contralateral projections from the anterior olfactory nucleus are present at birth but only appeared postnatally for the nucleus of the lateral olfactory tract. Numbers of olfactory bulb projecting neurons from the lateral entorhinal cortex, ventral hippocampus, and cortical amygdala show a sudden increase at the beginning of the second postnatal week and a delayed development compared to more anterior areas. These anatomical data suggest that limited top-down influence on odor processing in the olfactory bulb may be present at birth, but strongly increases during postnatal development and is only fully established later in life.