study-motor-skill-learning-by-single-pellet-reaching-tasks-in-mice

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and ...

University of California, Santa Cruz

Alterations in dendritic spine densities and morphologies have been correlated with the abnormal functioning of the synapse. Specifically the metabotropic glutamate receptor 5 (mGluR5) has been implicated in dendrogenesis and spineogenesis, since its activation triggers various signaling cascades that have been demonstrated to play roles in synaptic maturation and plasticity. Here we used the Golgi impregnation technique to analyze the dendritic spines of mGluR5(-/-) knockout mice in comparison to their heterozygote mGluR5(+/-) littermates. mGluR5(-/-) mice had elevated spine densities irrespective of spine type or location along their dendritic trees in comparison to mGluR5(+/-) animals. Such anatomical changes may underlie the hyperexcitability observed in mGluR5 total knockout mice.

mGluR5 knockout mice display increased dendritic spine densities.

Understanding the basic neuronal building blocks of the neocortex is a necessary first step toward comprehending the composition of cortical circuits. Neocortical layer VI is the most morphologically diverse layer and plays a pivotal role in gating information to the cortex via its feedback connection to the thalamus and other ipsilateral and callosal corticocortical connections. The heterogeneity of function within this layer is presumably linked to its varied morphological composition. However, so far, very few studies have attempted to define cell classes in this layer using unbiased quantitative methodologies. Utilizing the Golgi staining technique along with the Neurolucida software, we recontructed 222 cortical neurons from layer VI of mouse barrel cortex. Morphological analyses were performed by quantifying somatic and dendritic parameters, and, by using principal component and cluster analyses, we quantitatively categorized neurons into six distinct morphological groups. Additional systematic replication on a separate population of neurons yielded similar results, demonstrating the consistency and reliability of our categorization methodology. Subsequent post hoc analyses of dendritic parameters supported our neuronal classification scheme. Characterizing neuronal elements with unbiased quantitative techniques provides a framework for better understanding structure-function relationships within neocortical circuits in general.

Morphological heterogeneity of layer VI neurons in mouse barrel cortex.

The twenty-first annual Barrels meeting, sponsored by NINDS, was held on 12-14 November 2008 on the campus of Johns Hopkins University, near the site of the original discovery of barrels almost 40 years ago. The longest running satellite meeting to the Society for Neuroscience Annual Meeting focuses on the development, physiology, and behavior of the rodent whisker-to-barrel sensorimotor system. This year's event focused on what aspects of the sensory world are encoded by neurons within the system and how specifically the posterior medial nucleus can play a role in information processing. Other highlighted topics included the possible role(s) the cerebellum may have and the cues governing the patterning and development of thalamocortical inputs into the barrel cortex.

Barrels come of age: Barrels XXI meeting report.

Sex differences in systemic morphine analgesia occur with male rodents displaying significantly greater analgesic magnitudes and potencies than females. Neonatal androgenization, and to a lesser degree, adult ovariectomy enhance systemic morphine analgesia in female rats, implicating both organizational and activational effects of gonadal hormones. The neuroanatomical circuits sensitive to sex-related hormones by which females display a smaller opiate analgesic effect is not clear, but the ventromedial (VMH) and medial preoptic (MPOA) hypothalamic nuclei are critical in the monitoring of estradiol and other sex hormone levels. To assess the contribution of these nuclei to sex and adult gonadectomy differences in systemic morphine analgesia, intact male, intact female and adult ovariectomized (OVEX) female rats received bilateral saline (SAL) or ibotenic acid (IBO) microinjections into either the VMH or MPOA. Following surgeries, baseline tail-flick latencies over 120 minutes (min) were assessed over 4 days in all nine groups with intact females tested in the estrus phase of their cycle. All animals then received an ascending series of morphine (1.0, 2.5, 5.0, 7.5, 10.0mg/kg) injections 30min prior to the tail-flick test time course with 8-12 day inter-injection intervals between doses. Baseline latencies failed to differ between SAL-treated intact males and females, but were significantly higher in SAL-treated OVEX females. Both VMH IBO and MPOA IBO lesions increased baseline latencies in intact male and female rats, but not in OVEX females. SAL-treated intact males (ED(50)=4.0mg/kg) and SAL-treated OVEX females (ED(50)=3.5mg/kg) displayed significantly greater potencies of systemic morphine analgesia than SAL-treated intact females (ED(50)=6.3mg/kg), confirming previous gender and gonadectomy differences. Neither VMH IBO (ED(50)=3.7 mg/kg) nor MPOA IBO (ED(50)=4.1mg/kg) males differed from SAL-treated males in the potency of systemic morphine analgesia. In contrast, VMH IBO (ED(50)=4.1mg/kg) and MPOA IBO (ED(50)=3.5mg/kg) intact females displayed significantly greater potencies in systemic morphine analgesia than SAL-treated intact females. However, VMH IBO OVEX (ED(50)=3.5mg/kg) and MPOA IBO OVEX (ED(50)=3.9 mg/kg) failed to differ from SAL-treated OVEX females in the potency of systemic morphine analgesia. The magnitudes of systemic morphine analgesia as measured by Maximum Percentage Effect values displayed similar patterns, but lesser degrees, of effects. These data suggest that VMH and MPOA nuclei act to tonically inhibit endogenous pain-inhibitory circuits in the intact female, but not intact male brain, and that removal of circulating gonadal hormones by OVEX and/or excitotoxic destruction of these estrogen receptor accumulating nuclei disinhibit the female analgesic response to systemic morphine.

Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats.

Early postnatal sensory experience can have profound impacts on the structure and function of cortical circuits affecting behavior. Using the mouse whisker-to-barrel system we chronically deprived animals of normal sensory experience by bilaterally trimming their whiskers every other day from birth for the first postnatal month. Brain tissue was then processed for Golgi staining and neurons in layer 6 of barrel cortex were reconstructed in three dimensions. Dendritic and somatic parameters were compared between sensory-deprived and normal sensory experience groups. Results demonstrated that layer 6 non-pyramidal neurons in the chronically deprived group showed an expansion of their dendritic arbors. The pyramidal cells responded to sensory deprivation with increased somatic size and basilar dendritic arborization but overall decreased apical dendritic parameters. In sum, sensory deprivation impacted on the neuronal architecture of pyramidal and non-pyramidal neurons in layer 6, which may provide a substrate for observed physiological and behavioral changes resulting from whisker trimming.

Sensory deprivation differentially impacts the dendritic development of pyramidal versus non-pyramidal neurons in layer 6 of mouse barrel cortex.

Mesentery band-like adhesion which caused entrapment of duodenum at 32 gestational weeks.

To investigate flow in the ductus venosus at 11-13 + 6 weeks of gestation in women with normal pregnancies in the Taiwanese population.

Ductus venosus Doppler velocimetry in normal pregnancies from 11 to 13 + 6 weeks' gestation - a Taiwanese study.

Dendritic spines are small protrusions that serve as the principal recipients of excitatory inputs onto cortical pyramidal cells. Alterations in spine and filopodia density and morphology correlate with both developmental maturity and changes in synaptic strength. In order to better understand the developmental profile of dendritic protrusion (dendritic spines + filopodia) morphology and density over the animal's first postnatal year, we used the Golgi staining technique to label neurons and their dendritic protrusions in mice. We focused on quantifying the density per length of dendrite and categorizing the morphology of dendritic protrusions of layer VI pyramidal neurons residing in barrel cortex using the computer assisted reconstruction program Neurolucida. We classified dendritic protrusion densities at seven developmental time points: postnatal day (PND) 15, 30, 60, 90, 180, 270, and 360. Our findings suggest that the dendritic protrusions in layer VI barrel cortex pyramidal neurons are not static, and their density as well as relative morphological distribution change over time. We observed a significant increase in mushroom spines and a decrease in filopodia as the animals matured. Further analyses show that as the animal mature there was a reduction in pyramidal cell dendritic lengths overall, as well as a decrease in overall protrusion densities. The ratio of apical to basilar density decreased as well. Characterizing the profile of cortical layer VI dendritic protrusions within the first postnatal year will enable us to better understand the relationship between the overall developmental maturation profile and dendritic spine functioning.

Alterations of dendritic protrusions over the first postnatal year of a mouse: an analysis in layer VI of the barrel cortex.

Heterotopic triplet pregnancy with an intrauterine, a tubal, and a cervical gestation following in vitro fertilization and embryo transfer.

Abstract Corticothalamic (CT) feedback plays an important role in regulating the sensory information that the cortex receives. Within the somatosensory cortex layer VI originates the feedback to the ventral posterior medial (VPM) nucleus of the thalamus, which in turn receives sensory information from the contralateral whiskers. We examined the physiology and morphology of CT neurons in rat somatosensory cortex, focusing on the physiological characteristics of the monosynaptic inputs that they receive from the thalamus. To identify CT neurons, rhodamine microspheres were injected into VPM and allowed to retrogradely transport to the soma of CT neurons. Thalamocortical slices were prepared at least 3 days post injection. Whole-cell recordings from labeled CT cells in layer VI demonstrated that they are regular spiking neurons and exhibit little spike frequency adaption. Two anatomical classes were identified based on their apical dendrites that either terminated by layer V (compact cells) or layer IV (elaborate cells). Thalamic inputs onto identified CT-VPM neurons demonstrated paired pulse depression over a wide frequency range (2-20 Hz). Stimulus trains also resulted in significant synaptic depression above 10 Hz. Our results suggest that thalamic inputs differentially impact CT-VPM neurons in layer VI. This characteristic may allow them to differentiate a wide range of stimulation frequencies which in turn further tune the feedback signals to the thalamus.

Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons.

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex.

Article	Year
mGluR5 knockout mice display increased dendritic spine densities. Neuroscience letters\| PubMed ID: 22819970	2012
Morphological heterogeneity of layer VI neurons in mouse barrel cortex. The Journal of comparative neurology\| PubMed ID: 19065632	2009
Barrels come of age: Barrels XXI meeting report. Somatosensory & motor research\| PubMed ID: 19283554	2009
Ventromedial and medial preoptic hypothalamic ibotenic acid lesions potentiate systemic morphine analgesia in female, but not male rats. Behavioural brain research\| PubMed ID: 20678986	2010
Sensory deprivation differentially impacts the dendritic development of pyramidal versus non-pyramidal neurons in layer 6 of mouse barrel cortex. Brain structure & function\| PubMed ID: 21861159	2012
Mesentery band-like adhesion which caused entrapment of duodenum at 32 gestational weeks. Taiwanese journal of obstetrics & gynecology\| PubMed ID: 22212333	2011
Ductus venosus Doppler velocimetry in normal pregnancies from 11 to 13 + 6 weeks' gestation - a Taiwanese study. Journal of the Chinese Medical Association : JCMA\| PubMed ID: 22541146	2012
Alterations of dendritic protrusions over the first postnatal year of a mouse: an analysis in layer VI of the barrel cortex. Brain structure & function\| PubMed ID: 23779157	2013
Heterotopic triplet pregnancy with an intrauterine, a tubal, and a cervical gestation following in vitro fertilization and embryo transfer. Taiwanese journal of obstetrics & gynecology\| PubMed ID: 23915868	2013
Intrinsic properties of and thalamocortical inputs onto identified corticothalamic-VPM neurons. Somatosensory & motor research\| PubMed ID: 24397568	2014
The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex. Cerebral cortex (New York, N.Y. : 1991)\| PubMed ID: 24408954	2014

Chia-Chien Chen

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