Sarah Mikula - Academia.edu (original) (raw)

Papers by Sarah Mikula

ACS Applied Materials & Interfaces

Journal of Neuroscience, 2011

Changes in neuronal structure are thought to underlie long-term behavioral modifications associat... more Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain illdefined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons cotransfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that, in some instances, spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines.

The Journal of Comparative Neurology, 2009

High resolution 3D reconstruction and morphometric analysis of striosomes was carried out in maca... more High resolution 3D reconstruction and morphometric analysis of striosomes was carried out in macaque monkeys using immunocytochemistry for the Kv4 potassium channel subunit, KChIP1, a novel marker. The striosomes form a connected reticulum made up of two distinct planar sheets spanning several millimeters in the putamen, and long finger-like branches in the caudate nucleus and putamen. Although their spatial organization is variable, morphometric analysis of the striosomes, utilizing skeletonizations, reveals several quantitative invariant measures of striosome organization, including: 1) individual bifurcation-free striosome branches are 355±108.5 microns in diameter and 1013±751 microns in length, and are both lognormally distributed, and 2) striosome branches exhibit three pronounced orientation preferences that are approximately orthogonal. The former finding suggests a fundamental anatomical and functional component of the striatum, whereas the latter indicates that striosomes are more lattice-like than their spatial variability suggests. The perceived variable spatial organization of the striosomes in primates belies many invariant features that may reflect striatal function, development, and pathophysiology.

Hearing Research, 2006

Various animal models have been employed for otitis media research. The mouse has been studied le... more Various animal models have been employed for otitis media research. The mouse has been studied less, in spite of its many advantages. To better understand the suitability of the mouse for studies of otitis media, an evaluation was made of its middle ear inflammatory processes following inoculation with heat-killed Streptococcus pneumoniae (strain 6A), one of the three most common bacteria to cause otitis media in the human. A total of 94 BALB/c mice were injected transtympanically with three concentrations of heat-killed bacteria (10 4 , 10 6 , and 10 9 organisms per ml) and inflammation evaluated with both histologic examination and auditory brainstem response audiometry. Dose-related measures of the time course of inflammation showed it was maximal at 3 days. PBS-injected control mice also demonstrated some degree of middle ear inflammation. Therefore, inflammation measures from PBS injected mice were used as the threshold above which histologic inflammatory changes would be considered a response to bacteria. These quantitative comparisons of bacterial and PBS inoculations revealed the most significant middle ear measures of inflammation were amount of fluid in the middle ear, tympanic membrane thickness, and number of inflammatory cells. The induction of middle ear inflammation in the mouse demonstrated the applicability of this model for investigations of otitis media.

ACS Applied Materials & Interfaces

Journal of Neuroscience, 2011

Changes in neuronal structure are thought to underlie long-term behavioral modifications associat... more Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain illdefined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons cotransfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that, in some instances, spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines.

The Journal of Comparative Neurology, 2009

High resolution 3D reconstruction and morphometric analysis of striosomes was carried out in maca... more High resolution 3D reconstruction and morphometric analysis of striosomes was carried out in macaque monkeys using immunocytochemistry for the Kv4 potassium channel subunit, KChIP1, a novel marker. The striosomes form a connected reticulum made up of two distinct planar sheets spanning several millimeters in the putamen, and long finger-like branches in the caudate nucleus and putamen. Although their spatial organization is variable, morphometric analysis of the striosomes, utilizing skeletonizations, reveals several quantitative invariant measures of striosome organization, including: 1) individual bifurcation-free striosome branches are 355±108.5 microns in diameter and 1013±751 microns in length, and are both lognormally distributed, and 2) striosome branches exhibit three pronounced orientation preferences that are approximately orthogonal. The former finding suggests a fundamental anatomical and functional component of the striatum, whereas the latter indicates that striosomes are more lattice-like than their spatial variability suggests. The perceived variable spatial organization of the striosomes in primates belies many invariant features that may reflect striatal function, development, and pathophysiology.

Hearing Research, 2006

Various animal models have been employed for otitis media research. The mouse has been studied le... more Various animal models have been employed for otitis media research. The mouse has been studied less, in spite of its many advantages. To better understand the suitability of the mouse for studies of otitis media, an evaluation was made of its middle ear inflammatory processes following inoculation with heat-killed Streptococcus pneumoniae (strain 6A), one of the three most common bacteria to cause otitis media in the human. A total of 94 BALB/c mice were injected transtympanically with three concentrations of heat-killed bacteria (10 4 , 10 6 , and 10 9 organisms per ml) and inflammation evaluated with both histologic examination and auditory brainstem response audiometry. Dose-related measures of the time course of inflammation showed it was maximal at 3 days. PBS-injected control mice also demonstrated some degree of middle ear inflammation. Therefore, inflammation measures from PBS injected mice were used as the threshold above which histologic inflammatory changes would be considered a response to bacteria. These quantitative comparisons of bacterial and PBS inoculations revealed the most significant middle ear measures of inflammation were amount of fluid in the middle ear, tympanic membrane thickness, and number of inflammatory cells. The induction of middle ear inflammation in the mouse demonstrated the applicability of this model for investigations of otitis media.