Anna Lysakowski

Anna Lysakowski
University of Illinois at Chicago | UIC · Department of Anatomy and Cell Biology (Chicago)

Ph.D.

About

77
Publications
11,776
Reads
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Introduction
We have 4 projects in the laboratory now: 1) molecular and immunohistochemical characterization of the vestibular calyx afferent, including voltage-gated ion channels, glutamate and potassium co-transporters; 2) a study of the ultrastructural and protein structure of a cytoskeletal striated organelle present in all inner ear hair cells, except cochlear outer hair cells; 3) an investigation of the structure and function of inner ear mitochondria; and 4) genetics of Meniere's Disease.
Additional affiliations
March 2014 - September 2014
Glasgow School of Art
Position
  • US-UK Fulbright Scholar - Visiting Scholar (3D Medical Visualization)
November 2010 - December 2010
Universitätsmedizin Göttingen - Georg-August-Universität Göttingen
Position
  • Researcher
Description
  • Sabbatical
June 1993 - March 2020
University of Illinois at Chicago
Position
  • Professor (Assistant)
Education
January 1985 - December 1990
The University of Chicago
Field of study
  • Neurobiology
August 1979 - December 1984
University of Illinois at Chicago
Field of study
  • Anatomy (specializing in Neuroanatomy and Cell Biology)

Publications

Publications (77)
Article
Full-text available
The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly under...
Article
Full-text available
Many primary vestibular afferents form large cup-shaped postsynaptic terminals (calyces) that envelope the basolateral surfaces of type I hair cells. The calyceal terminals both respond to glutamate released from ribbon synapses in the type I cells and initiate spikes that propagate to the afferent's central terminals in the brainstem. The combinat...
Article
Full-text available
The striated organelle (SO), a cytoskeletal structure located in the apical region of cochlear and vestibular hair cells, consists of alternating, cross-linked, thick and thin filamentous bundles. In the vestibular periphery, the SO is well developed in both type I and type II hair cells. We studied the 3D structure of the SO with intermediate-volt...
Article
Meniere’s Disease (MD) is a complex disorder associated with an accumulation of endolymph in the membranous labyrinth in the inner ear. It is characterized by recurrent attacks of spontaneous vertigo associated with sensorineural hearing loss (SNHL) and tinnitus. The SNHL usually starts at low and medium frequencies with a variable progression to h...
Preprint
Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal referred to as a calyx. The vestibular hair cell-calyx synapse supports nonquantal transmission (NQT), a neurotransmitter...
Article
Full-text available
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, ER, and plasma membrane promote regulation of multiple functions, which include intracellular Ca²¹ flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related...
Article
Full-text available
Naked mole-rats are highly vocal, eusocial, subterranean rodents with, counterintuitively, poor hearing. The causes underlying their altered hearing are unknown. Moreover, whether altered hearing is degenerate or adaptive to their unique lifestyles is controversial. We used various methods to identify the factors contributing to altered hearing in...
Chapter
Synopsis The vestibular system has two types of hair cells that detect head motion and three morphological types of vestibular afferents that transmit this information to the brain, where it is used in several important reflexes, vestibulo-ocular, vestibulo-collic, vestibulo-spinal and vestibulo-autonomic reflexes, to name a few. Some of these refl...
Chapter
Synopsis This chapter covers a number of topics related to the anatomy and microstructural organization of vestibular hair cells, from types of hair cells and afferents, to the development of the sensory epithelium, to cell biology of hair cells (including the striated organelle, mitochondria and ribbon synapses), to some membrane properties that r...
Article
In several systems of the body (muscle, liver, nerves), new studies have examined the internal structure of mitochondria and brought to light striking new findings about how mitochondria are constructed and how their structure affects cell function. In the inner ear field, however, we have little structural knowledge about hair cell and supporting...
Article
Objective The goal of this work is to study the changes in white matter integrity in R6/2, a well-established animal model of Huntington’s disease (HD) that are captured by ex vivo diffusion imaging (DTI) using a high field MRI (17.6 T). Materials and methods DTI and continuous time random walk (CTRW) models were used to fit changes in the diffusi...
Article
Full-text available
Significance statement: Targeting the efferent vestibular system (EVS) pharmacologically might prove useful in ameliorating some forms of vestibular dysfunction by modifying ongoing primary vestibular input. EVS activation engages several kinetically-distinct, synaptic processes that profoundly alter the discharge rate and sensitivity of first-ord...
Article
Full-text available
Little is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout mice, α10 knockout mice, α7 knockout mice, α9/10 and α7/9 double knockouts, and wild type controls. We also studied the morphology and ultrastructure of efferent termin...
Chapter
The survival of vertebrates is dependent on maintaining their body equilibrium in the gravitational field and being capable of orienting themselves in their environment. Studies have demonstrated that well-defined neuronal networks in the central nervous system implement these complex sensorimotor transformations, known as the vestibuloocular, cerv...
Article
Full-text available
Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the...
Article
Full-text available
Meniere's disease is a chronic disorder of the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo, and familial Meniere's disease is observed in 5-15% of sporadic cases. Although its pathophysiology is largely unknown, studies in human temporal bones have found an accumulation of endolymph in the scala media of the cochl...
Article
Full-text available
Thermolysin is a metallopeptidase used to cleave peptide bonds at specific junctions. It has previously been used to cleave specific amino acid sequences found at the junction of the sensory epithelium and underlying stroma of unfixed otolithic organs of the vestibular system. We have used thermolysin to separate sensory epithelium from the underly...
Conference Paper
Full-text available
In the dental curriculum, the initial administration of local anaesthesia injection on live patients is critical and students may experience a high degree of anxiety. Low self-confidence often caused by insufficient knowledge of anatomy has been repeatedly reported as one of the major causes. In this paper, we focus on the development of a haptic t...
Article
Full-text available
Glutamate is the neurotransmitter released from hair cells. Its clearance from the synaptic cleft can shape neurotransmission and prevent excitotoxicity. This may be particularly important in the inner ear and in other sensory organs where there is a continually high rate of neurotransmitter release. In the case of most cochlear and type II vestibu...
Article
Full-text available
Various studies point to a crucial role of the high-affinity sodium-coupled glutamate aspartate transporter GLAST-1 for modulation of excitatory transmission as shown in the retina and the CNS. While 2-4-month-old GLAST-1 null mice did not show any functional vestibular abnormality, we observed profound circling behavior in older (7 months) animals...
Chapter
Full-text available
As is the case with most hair-cell organs, the vestibular labyrinth receives a dual innervation. Afferent nerve fibers arise from bipolar cells in the vestibular (Scarpa’s) ganglion. The peripheral process of each ganglion cell gets synaptic inputs from hair cells in one of several discrete organs, and its central process conveys the resulting info...
Presentation
The striated organelle (STO) is a structure located in the subcuticular region of hair cells, consisting of alternating thick and thin bands (Friedman, 1965; Ross and Bourne, 1983). Although present in all cochlear and vestibular hair cells, the STO is particularly well-developed in type I hair cells, where it is shaped like an inverted open cone t...
Article
Type I hair cells outnumber type II hair cells (HCs) in squirrel monkey (Saimiri sciureus) cristae by a nearly 3:1 ratio. Associated with this type I HC preponderance, calyx fibers make up a much larger fraction of the afferent innervation than in rodents (Fernández et al. [1995] J. Neurophysiol. 73:1253-1269). To study how this affects synaptic ar...
Article
Full-text available
Intracellular recordings were made from nerve fibers in the posterior ampullary nerve near the neuroepithelium. Calyx-bearing afferents were identified by their distinctive efferent-mediated responses. Such fibers receive inputs from both type I and type II hair cells. Type II inputs are made by synapses on the outer face of the calyx ending and on...
Article
Full-text available
Two kinds of sodium current (I(Na)) have been separately reported in hair cells of the immature rodent utricle, a vestibular organ. We show that rat utricular hair cells express one or the other current depending on age (between postnatal days 0 and 22, P0-P22), hair cell type (I, II, or immature), and epithelial zone (striola vs. extrastriola). Th...
Article
Full-text available
To study the cellular mechanisms of efferent actions, we recorded from vestibular-nerve afferents close to the turtle posterior crista while efferent fibers were electrically stimulated. Efferent-mediated responses were obtained from calyx-bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents distinguished by their neuroepitheli...
Article
Full-text available
Hearing and balance rely on the faithful synaptic coding of mechanical input by the auditory and vestibular hair cells of the inner ear. Mechanical deflection of their stereocilia causes the opening of mechanosensitive channels, resulting in hair cell depolarization, which controls the release of glutamate at ribbon-type synapses. Hair cells have a...
Article
Full-text available
Type I vestibular hair cells have large K+ currents that, like neuronal M currents, activate negative to resting potential and are modulatable. In rodents, these currents are acquired postnatally. In perforated-patch recordings from rat utricular hair cells, immature hair cells [younger than postnatal day 7 (P7)] had a steady-state K+ conductance (...
Article
Full-text available
Adaptor protein 3 (AP-3) is a vesicle-coat protein that forms a heterotetrameric complex. Two types of AP-3 subunits are found in mammalian cells. Ubiquitous AP-3 subunits are expressed in all tissues of the body, including the brain. In addition, there are neuronal AP-3 subunits that are thought to serve neuron-specific functions such as neurotran...
Chapter
Full-text available
With the development of intraaxonal labeling methods, it has become possible to relate the discharge properties of a vestibular afferent with its peripheral innervation patterns. In this chapter, we review the results of such morphophysiological studies. To provide a context for the review, we first consider the morphology of the vestibular organs...
Article
Vestibular tissues (cristae ampullares, macular otolithic organs, and Scarpa's ganglia) in chinchilla, rat, and guinea pig were examined for immunoreactivity to the alpha9 nicotinic acetylcholine receptor (nAChR) subunit. The alpha9 antibody was generated against a conserved peptide present in the intracellular loop of the predicted protein sequenc...
Article
Full-text available
The quantal hypothesis states that neurotransmitter is released in discrete packages, quanta, thought to represent the neurotransmitter content of individual vesicles. If true, then vesicle size should influence quantal size. Although chromaffin cells are generally thought to have a single population of secretory vesicles, our electron microscopy a...
Article
Full-text available
Calyx afferents, a group of morphologically and physiologically distinct afferent fibers innervating the striolar region of vestibular sensory epithelia, are selectively labeled by antibodies to the calcium-binding protein calretinin. In this study, the population of calretinin-stained calyx afferents was used to delineate and quantify the striolar...
Article
We made flattened neuroepithelial preparations of horizontal and vertical (anterior and posterior) cristae from mouse, rat, gerbil, guinea pig, chinchilla, and tree squirrel. Calretinin immunohistochemistry was used to label the calyx class of afferents. Because these afferents are restricted to the central zone of the crista, their distribution al...
Article
Full-text available
We have previously shown that there is a slowly progressing, frequency-specific recovery of the gain and phase of the horizontal vestibuloocular reflex (VOR) in rhesus monkeys following plugging of the lateral semicircular canals. The adapted VOR response exhibited both dynamic and spatial characteristics that were distinctly different from respons...
Article
Full-text available
BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the develo...
Article
Efferent innervation of the vestibular labyrinth is known to be cholinergic. More recent studies have also demonstrated the presence of the neuropeptide calcitonin gene-related peptide in this system. Nitric oxide is one of a new class of neurotransmitters, the gaseous transmitters. It acts as a second messenger and neurotransmitter in diverse phys...
Article
Full-text available
Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using...
Chapter
The purpose of this paper is to review some of the recent concepts in the anatomy of the vestibular periphery related to equilibrium regulation. Ultrastructural results from our laboratory that build upon recent morphophysiological studies are presented. Among the ultrastructural findings presented are differences in cytoarchitecture (including hai...
Article
Full-text available
The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak v...
Article
Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Perip...
Article
To determine whether there are anatomical correlates for intraterminal Ca2+ stores to regulate exocytosis of dense-cored vesicles (DCVs) and whether these stores can modulate exocytosis of synaptic vesicles, we studied the spatial distributions of DCVs, smooth endoplasmic reticulum (SER), and mitochondria in 19 serially reconstructed nerve terminal...
Article
Two morphological classes of mechanosensory cells have been described in the vestibular organs of mammals, birds, and reptiles: type I and type II hair cells. Type II hair cells resemble hair cells in other organs in that they receive bouton terminals from primary afferent neurons. In contrast, type I hair cells are enveloped by large cuplike affer...
Article
Full-text available
The type I and type II hair cells of mature amniote vestibular organs have been classified according to their afferent nerve terminals: calyx and bouton, respectively. Mature type I and type II cells also have different complements of voltage-gated channels. Type I cells alone express a delayed rectifier, gK,L, that is activated at resting potentia...
Article
The chinchilla crista ampullaris was studied in 10 samples, each containing 32 consecutive ultrathin sections of the entire neuroepithelium. Dissector methods were used to estimate the incidence of various synaptic features, and results were confirmed in completely reconstructed hair cells. There are large regional variations in cellular and synapt...
Conference Paper
The chinchilla vestibular nerve consists of three morphologically defined classes of afferents. Calyx afferents are thick fibers ending with chalice-shaped terminals on type I hair cells in the central zone of the sensory epithelium. Bouton afferents are thin fibers ending with bouton terminals on type II hair cells in the peripheral zone. Dimorphi...
Article
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Article
Full-text available
1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas....
Article
Full-text available
1. Semicircular-canal afferents in the squirrel monkey were characterized by their resting discharge, discharge regularity, sensitivity to galvanic currents delivered to the ear (beta *), the gain (g2Hz), and phase lead (phi 2Hz) of their response to 2-Hz sinusoidal head rotations, and their antidromic conduction velocity. Discharge regularity was...
Article
There are three kinds of afferent terminations in the cristae ampullares. Calyx units innervate a few neighboring type I hair cells. Bouton units contact several type II hair cells. Dimorphic units innervate both kinds of receptors. Axon diameters are largest for calyx fibers and smallest for bouton fibers. Dimorphic units supply all parts of the s...
Article
The distribution of cholinergic fibers in rat cortex was investigated using choline acetyl-transferase immunohistochemistry. Previous studies have either shown differences in distribution, but have been limited to selected areas, or have shown no discernable differences between different cortical areas. In our study, we examined all areas of rat co...