Mitral Cell Dendritic Development in the Mouse Main Olfactory Bulb

Correct targeting and differentiation of the mitral cell (MC) dendrites in the olfactory bulb (OB) is clearly essential for development of functional neuronal circuits. MCs, the primary OB projection neurons, receive odor information from OSN axons via axodendritic synapses on their apical dendrite; the signal is further processed via dendrodendritic synapses on MC lateral dendrites. In the adult, each MC cell apical dendrite targets a single glomerulus, ending in a characteristic glomerular tuft and receiving input from molecularly defined subsets of OSNs. MC lateral dendrites segregate deep to the glomerular layer, in a sublamina of the external plexiform layer. MC dendrites are initially undifferentiated and often supernumerary; the adult form of one apical and several lateral dendrites emerges postnatally. We sought to define more clearly the emergence of MC apical versus lateral dendrites using DiI fills. We also used a dendritic growth cone specific antibody, CDA 1 to assess spatiotemporal patterns of development in the OB. MCs progressed through a broad spectrum of transitional morphologies from a broadly spread arbor of supernumerary dendrites in the embryo to the single apical dendrite and lateral dendrites characteristic of the adult. At P0, MCs exhibit the immature dendritic morphology with a broadly spread arbor of a large number of relatively uniform dendrites. By P1, this arbor appears to have narrowed and one dendrite appears thicker than the others, probably on its way to differentiating into an apical dendrite. At P4, two clearly distinguishable subpopulations of neurons have clearly emerged, but some cells exhibit two apical dendrites. By P8, MCs appear to have an adult dendritic morphology. Quantitative analysis of CDA 1 expression patterns in the OB at postnatal day 0, 2, 4, 8, suggests intra- and interlaminar patterns of dendritic development. Preliminary data further suggest distinct temporal windows of MC dendritic development along the rostrocaudal axis. CDA 1 expression in all laminae decreases significantly by postnatal day 8 and appears indistinguishable from background in the adult. Thus, both lines of data show evidence of significant postnatal dendritic remodeling

Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways

Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50 dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320 Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50 Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals

Inducing Neural Plasticity and Modulation Using Multisensory Stimulation: Techniques for Sensory Disorder Treatment

University of Minnesota Ph.D. dissertation. June 2017. Major: Biomedical Engineering. Advisor: Hubert Lim. 1 computer file (PDF); xvi, 245 pages.In this dissertation, we characterized the modulatory and plasticity effects of paired multisensory stimulation on neural firing in sensory systems across the brain. In the auditory system, we discovered that electrical somatosensory stimulation can either suppress or facilitate neural firing in the inferior colliculus (IC) and primary auditory cortex (A1) depending stimulation location. We also tested plasticity effects in A1 in response to paired somatosensory and acoustic stimulation with different inter-stimulus delays in anesthetized guinea pigs, and found that plasticity induced by paired acoustic and right mastoid stimulation was consistently suppressive regardless of delay, but paired acoustic and pinna stimulation was timing-dependent, where one inter-stimulus delay was consistently suppressive while other delays induced random changes. These experiments were repeated in awake animals with paired acoustic and pinna stimulation, and two animal groups of different stress levels were used to assess stress effects on plasticity. We found that in low-stress animals, the same inter-stimulus delay was consistently suppressive and a neighboring delay was consistently facilitative across all animals, which matches previous invasive spike-timing dependent plasticity studies (anesthesia may have affected these trends). Meanwhile, high-stress animal results were not consistent with expected time dependence and exhibited no trends across inter-stimulus delays, indicating that stress can have adverse effects on neuromodulation plasticity outcomes. In all other primary sensory cortices, we found that differential effects can be induced with paired sensory stimulation such that the location, amount, type, and timing of plasticity can be controlled by strategically choosing sensory stimulation parameters for modulation of each sensory cortex. We also investigated the ability to target subpopulations of neurons within a brain region and found that by stimulating at levels near activation thresholds, specific subpopulations of IC neurons can be targeted by varying somatosensory stimulation location. Furthermore, acoustic stimulation can excite or modulate specific areas of somatosensory cortex, and we mapped the guinea pig homunculus to characterize this. Overall, these findings illustrate the immense interconnectivity between sensory systems, and multisensory stimulation may provide a noninvasive neuromodulation approach for inducing controlled plasticity to disrupt pathogenic neural activity in neural sensory disorders, such as tinnitus and pain

Electrophysiological profile and monosynaptic circuitry of efferent vestibular nucleus neurons

As with other sensory modalities, the vestibular system recruits efferent circuitry to transport information from the central nervous system (CNS) to the sensory periphery. This efferent vestibular system (EVS) originates in the brainstem and terminates on vestibular hair cells and afferent fibres in the semicircular canals and otolith organs. Understanding how this central component outputs to the vestibular organs, and mediates motor and vestibular coordination, could potentially impact clinical treatment of vestibular disorders. Previous EVS work has primarily focused on the anatomy, pharmacology, synaptic mechanisms, and peripheral effects of efferent vestibular nucleus (EVN) activation. Although this work is fundamental to understanding this system and its mechanism of action, the behavioural function of the EVS is yet to be ascribed. For this, we need to appreciate the physiology of EVN neurons, and their context of activation within the CNS. In this thesis, I characterise the electrophysiological profile of EVN neurons, and trace their direct monosynaptic circuitry. My methodology includes whole-cell current- and voltage- clamp electrophysiology, and glycoproteindeficient rabies virus tracing techniques. Using these, I enrich understanding of EVN action, and hint at potential functional roles from their CNS partners. The data presented in this thesis provides novel insights into the EVS. EVN neurons are characterised with a homogeneous output, but a heterogeneous synaptic input profile. Inputs to the EVN originate from diverse areas in the brainstem and cortex. These findings suggest that the EVN modulates vestibular end organs in multiple different behavioural contexts. This work forms the basis of subsequent EVS behavioural investigations such as loss of function experiments targeting input regions via optogentic means and subsequent EVS recordings, or silencing of EVN activity and subsequent behavioural testing. Collectively, my results, these future directions, and the existing body of EVS literature, brings us closer than ever to understanding and ascribing a functional role for the EVS

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 128, May 1974

This special bibliography lists 282 reports, articles, and other documents introduced into the NASA scientific and technical information system in April 1974

Neuroanatomical and gene expression features of the rabbit accessory olfactory system. Implications of pheromone communication in reproductive behaviour and animal physiology

Mainly driven by the vomeronasal system (VNS), pheromone communication is involved in many species-specific fundamental innate socio-sexual behaviors such as mating and fighting, which are essential for animal reproduction and survival. Rabbits are a unique model for studying chemocommunication due to the discovery of the rabbit mammary pheromone, but paradoxically there has been a lack of knowledge regarding its VNS pathway. In this work, we aim at filling this gap by approaching the system from an integrative point of view, providing extensive anatomical and genomic data of the rabbit VNS, as well as pheromone-mediated reproductive and behavioural studies. Our results build strong foundation for further translational studies which aim at implementing the use of pheromones to improve animal production and welfare

Network interactions of medial prefrontal cortex, hippocampus and reuniens nucleus of the midline thalamus

Le présent mémoire corrobore l'hypothèse selon laquelle l'hippocampe, le cortex préfrontal et le noyau reuniens du thalamus constituent un réseau fonctionnel dans lequel le noyau reuniens servirait d'interfacé entre l'hippocampe et le cortex pré frontal. Bien que la voie hippocampo-corticale de ce réseau ait été abondamment étudiée, cela n'est pas le cas pour la voie reuniens-préfrontale. Nous décrivons ici, pour la première fois, la réponse de neurones du cortex préfrontal médian aux stimulations du noyau reuniens. Chez des chats sous anesthésie (kétamine-xylazine), nous avons effectué simulatanément 1) des enregistrements intra- et extracellulaires dans le cortex préfrontal médian et 2) des stimulations du noyau reuniens ou de l'hippocampe à l'aide d'électrodes bipolaires. Nous avons ainsi démontré que la réponse de neurones du cortex préfrontal médian aux stimulations du noyau reuniens est distincte des réponses évoquées par des stimulations hippocampiques, que la voie reuniens-préfrontale est sujette à la plasticité à court terme et qu'une région restreinte du cortex préfrontal médian sert de relai à la voie hippocampo-cortico-thalamique

Noradrenergic Modulation of Lateral Geniculate Neurons: Physiological and Pharmacological Studies

The physiological actions of norepinephrine (NE) were examined in the rat dorsal lateral geniculate nucleus (LGNd) using extracellular single cell recording and microiontophoresis. Prolonged, low current iontophoretic applications of NE consistently elicited an increase in the firing rate of LGNd neurons which was delayed in onset and prolonged after cessation of the ejection. Sympathomimetic amines other than NE also activated LGNd neurons with varying degrees of effectiveness. On the basis of the relative potencies of a series of these agonists and the ability of iontophoretically applied (alpha)-antagonists to selectively block the facilitatory action of NE, it is concluded that NE acts via an (alpha)(,1)- ( postsynaptic ) adrenoceptor. Systemic administration of the (alpha)-adrenoceptor antagonist WB-4101 also produced a selective blockade of the response to NE. In contrast to NE, serotonin (5-HT) produced a suppression of the firing of LGNd neurons.To examine the effects of NE on evoked activity, identified geniculocortical relay neurons (P-cells) were driven by electrical stimulation of the afferent visual pathway at the level of the optic chiasm. NE caused a marked facilitation of both the short latency (2-4 msec) and the delay (70-230 msec) responses to such stimulation. The (alpha)-adrenoceptor antagonist phentolamine, which by itself had no consistent effect on evoked activity, strongly diminished the response to NE. 5-HT was a powerful depressant of electrically evoked activity; neither phentolamine nor the 5-HT antagonist methysergide antagonized this response. Firing of LGNd units evoked by flashes of light was also facilitated by NE and depressed by 5-HT.When afferent excitation from the retina was eliminated by enucleation of the eyes, many LGNd neurons ceased firing spontaneously. Silent neurons in enucleated animals generally did not respond to NE although the excitatory amino acid glutamate was still highly active. Under these conditions, NE enhanced the excitation produced by glutamate, suggesting that NE increases the general excitability of these neurons and that it acts in a neuromodulatory fashion. The (gamma)-aminobutyric acid (GABA) antagonist picrotoxin, unlike NE, did not facilitate the action of glutamate, indicating that the action of NE is not mediated by suppression of adjacent GABAergic interneurons.Electrical stimulation of the locus coeruleus (LC), which contributes a dense noradrenergic innervation to the LGNd, mimicked the activating effect produced by locally applied NE. The response to 10 Hz trains was generally delayed and the increased rate persisted after the stimulation period. This effect was blocked by iontophoretic application or intravenous administration of WB-4101. Silent cells in enucleated animals were not activated by LC stimulation, but, as with iontophoretic NE, LC stimulation did facilitate the excitatory action of glutamate. WB-4101 blocked both the facilitatory actions of LC stimulation and of iontophretic NE.It is concluded that NE, action via an (alpha)(,1)-adrenoceptor, facilitates the excitability of LGNd relay neurons to afferent stimulation. The close similarity between the effects of locally applied NE and stimulation of the LC provided evidence that NE is a transmitter in the coeruleogeniculate pathway. This pathway may serve to modulate the transmission of visual information from the retina to the strate cortex