No description available.

No description available.

No description available.

Diss.--Philosophische Fakultät--Köln--Universität, 1990.

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009. / Title from title page screen (viewed on September 18, 2009). Research advisor: Robert W. Williams, Ph.D. Document formatted into pages (ix,128 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 106-127).

Thesis (Ph. D.)--Drexel University, 2006. / Includes abstract and vita. Includes bibliographical references (leaves 127-162).

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Guang R. Gao, Dept. of Electrical and Computer Engineering. Includes bibliographical references.

<p>In mammals, the perception of smell starts with the activation of odorant receptors (ORs) by volatile molecules in the environment. Mammalian genomes typically encode large numbers of ORs, with approximately 400 intact ORs in human and more than 1000 in mouse. Central to the question of how olfactory stimuli are represented at the peripheral level is defining the ligand selectivity and activity regulation of ORs.</p><p>Processing of chemosensory signals in the brain is dynamically regulated in part by an animal’s physiological state. The Matsunami lab previously reported that type 3 muscarinic acetylcholine receptors (M3-Rs) physically interact with odorant receptors (ORs) to promote odor-induced responses in a heterologous expression system. However, it is not known how M3-Rs affect the ability of olfactory sensory neurons (OSNs) to respond to odors. In chapter 2, I demonstrate that the activation of M3-Rs inhibits the recruitment of β-arrestin-2 to ORs, resulting in a potentiation of odor-induced response in OSNs. These results suggest a role for acetylcholine in modulating olfactory processing at the initial stages of signal transduction in the olfactory system.</p><p>Understanding odor coding requires comprehensive mapping between odorant receptors and corresponding odorants. In chapter 3, I present a high-throughput in vivo method to identify repertoires of odorant receptors activated by odorants, using phosphorylated ribosome immunoprecipitation of mRNA from olfactory epithelium of odor-stimulated mice followed by RNA-Seq. This approach screens endogenously expressed odorant receptors against an odorant in one set of experiments, using awake and freely behaving mice. In combination with validations in a heterologous system, we identify sets of odorant receptors for two odorants, acetophenone and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), encompassing 69 receptor-odorant pairs. I also identified shared amino acid residues specific to the acetophenone or TMT receptors, and developed a model to predict receptor activation. This study provides a means to understand the combinatorial coding of odors in vivo.</p> / Dissertation

<p>Animals must continuously move through the environment in pursuit of the goals required to maintain homeostasis. In vertebrates, this is accomplished through an ever-changing pattern of muscle contraction in a multipurpose body, and coordinated by a hierarchy of neural circuits acting in parallel. At the lower levels of this hierarchy, spinal circuits control muscle force and length. One level above that, brainstem, midbrain and cortical circuits control various aspects of body configuration as well as a number of self-contained motor functions including locomotion and orientation. A still-higher level of organization is controlled by the basal ganglia, a set of subcortical nuclei that appear to be responsible for continuously orchestrating the extent and direction of various motor programs and body configurations for the sake of controlling a still higher level of perceptual variable, such as proximity to food. In this way, the basal ganglia orchestrate the performance of motor functions to achieve a single goal in the same way that a conductor orchestrates the performance of musicians in a symphony to achieve a single song. </p><p>Despite the continuous and graded nature of animal behavior, researchers have traditionally studied the basal ganglia in the context of highly controlled experimental tasks or neglected to record continuous measures of behavioral outputs. To address this gap, the following experiments were designed investigate role of the basal ganglia in continuously modulating unconstrained goal directed movements. In the first set of experiments (chapter 2), mice stood on a small covered perch which was continuously tipped left and right along the roll plane while neural activity was recorded wirelessly. During each recording session, mice were exposed to slow and fast speeds of postural disturbance. Pressure pads were mounted in the left and right floor of the perch to monitor mouse movement. In both putative dopamine and GABA neurons, we found two basic patterns of neural activity; one class of cell increased firing with tip to the left and decreased with tip to the right while the other class decreased firing with tip to the left and increased with tip to right. This correlation between neural firing rate and instantaneous postural disturbance is continuous and very high. The correlation is seen for both slow and fast disturbances. The majority of cells recorded fell into one of these two categories. Pressure pad readout, as expected, revealed paw forces on the left pad to increase with tilt to the left and decrease with tilt to the right while the opposite pattern was observed on the right pad. These results show continuous and graded modulation of activity in the substantia nigra during performance of an ongoing motor task and suggest that BG outputs, rather than monolithically disinhibiting brainstem motor structures, instead coordinate behavior by continuously specifying desired states of lower systems. </p><p>In the second set of experiments (chapter 3), we employed continuous motion tracking of the head in parallel with neural recording from the substantia nigra pars reticulata during a simple goal-directed task. In this study, mice were water deprived and then positioned on a perch equipped with a movable drinking spout. During each session, mice performed a simple reward-guided task in which sucrose solution was delivered in small quantities after the presentation a cue. The purpose of this task was to elicit voluntary head movements and to investigate the relationship between these continuous movements and the activity of GABA output neurons. A typical reward-directed behavior involved the movement of the whole head and body to collect the sucrose solution following its delivery. However, movements during each individual trial were unique. For all movements, the majority of GABA cells were found to either positively or negatively correlate with either X or Y axis head position vector components. These correlations were very high, and not due to averaging artifacts as trial-by-trial correlation between movement and neural activity can be clearly observed. These correlations were also independent of the presence of a reward. These data show for the first time a continuous and quantitative relationship between basal ganglia output and body posture. It is hypothesized that these signals represent reference signals sent to downstream postural and orientation controllers. In this case a baseline level of GABA activity would represent neutral reference position, and changes in activity above and below this level represent increased or decreased reference positions. </p><p>In the third set of experiments (chapter 4), we recorded from dopamine neurons in the substantia nigra pars compacta during the same task as in chapter 3. The purpose of this task was to investigate the correlation between dopamine activity and movement kinematics during goal-directed behavior. Animals were found to produce movements at the onset of the cue and also at reward delivery. Dopamine-classified cells show phasic firing or pausing at the onset of each of these movements. When compared to head movement kinematics, these patterns of neural activity correlate highly with different vector components of head acceleration and velocity; up, down, left and right. Importantly, these correlations are continuous and exist throughout the entire recording session. These correlations are also independent of the presence of reward. To test the ‘causality’ of these observed patterns, we also employed optogenetics to stimulate substantia nigra dopamine neurons expressing channel rhodopsin 2 (Chr2) while head movements were recorded and quantified. We found that stimulation of ChR2-expressing animals could elicit head movement while stimulation of control animals had no effect. Combined, these data suggest that dopamine is responsible for controlling the velocity of transitions between different body postures.</p> / Dissertation

The spatial arrangement of neuronal responses in primary auditory cortex (A1) has so far been investigated by using microelectrode recording techniques or imaging of the intrinsic signal, which led to controversial results, at present still discussed. On the other hand, two-photon calcium imaging allows us to investigate the cortical functions at an unprecedented level of spatial detail, and has recently offered new insight into the fine-scale organization of frequency responses in A1. In this thesis, I used two-photon calcium imaging to compare, for the first time, the fine-scale cortical representation of sound frequency to that of two other sound features, crucial for survival and communication in all mammals: differences in intensity between the two ears (interaural level differences; ILDs), and frequency modulation (FM). I found that most neurons in layers II-III of the mouse A1 were tuned to ILDs favouring the contralateral ear, but midline and ipsilateral tuning were present too. Binaural preferences were heterogeneously distributed in space, both on the fine scale (within &Tilde; 200 &mu;m) and on the global one (up to &Tilde; 1 mm). Moreover, A1 neurons were mostly tuned to slow FM sweeps within the range of those used in species-specific calls. Cells activated by similar rates tended to be spatially proximal, indicating a level of local organization similar to the one I found for frequency tuning, and higher than that of ILD responses. Finally, I set the groundwork for two-photon studies of the A1 of the ferret, by presenting the first evidence of the microscopic organization of the tonotopic map in this species. My results shed light on some long-held questions about the response properties of A1, and confirm two-photon imaging as a powerful tool for investigating the processing of sensory signals in the cortex of both small and large mammals.