<p> Cellular level learning is vital to almost all brain function, and extensive homeostatic plasticity is required to maintain brain functionality. While much has been learned about cellular level plasticity <i>in vivo,</i> how these mechanisms affect higher level functionality is not readily apparent. The cellular level circuitry of most networks that process information is unknown. A variety of models were developed to better understand plasticity in both learning and homeostasis. </p><p> Spike time dependent plasticity (STDP) and reward-modulated plasticity may be the primary methods through which neurons record information. We implemented rewarded STDP to model foraging behavior in a virtual environment. When appropriate homeostatic mechanisms were in place, the network of spiking neurons developed the capability of producing highly successful decision-making. </p><p> The networks used in the foraging model used a very simple initial configuration to avoid assumptions about network organization. More realistic network configurations can help to show how plasticity interacts with genetically determined network. We developed three network models of synaptic mechanisms of FM sweep processing based on published experimental data. One of these, the 'inhibitory sideband' model, used frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections resulted in neurons responsive to sweeps in a single direction and of sufficient rate. STDP was shown to be capable of causing to become selective for sweeps in the same direction as a repeatedly presented training sweep. </p><p> The experience dependent plasticity, occurs primarily during the waking state, however, sleep is essential for learning. Slow wave sleep activity may be essential for memory consolidation and homeostasis. We developed a model of slow wave sleep that included methods to calculate the electrical field in the space around the network. We show here that a network model of up and down states displays this CSD profile only if a frequency-filtering extracellular medium is assumed. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the it's termination remains poorly understood. We explored the impact of intrinsic and synaptic inhibition on the state transition. We found that synaptic inhibition controls the duration and the synchrony of active state termination. </p><p> Together these models set the stage for a model network that can learn through input driven processes in a waking state then explore the consolidation of memory in a sleeping state. This will allow us to explore in greater detail how plasticity on the level of a single cell contributes to learning and stability on the level of the whole brain.</p>

Differences in the behavior of excitable cells are correlated with differences in function. The electrical properties of a neuron are primarily determined by the array of potassium channels that it expresses. These experiments examined potassium currents in two populations of neurons from the chick embryo. Neurons from the parasympathetic ciliary ganglion can fire action potentials at a very high rate, while neurons from the lumbar sympathetic chain ganglia have a much lower maximum firing rate. The results show that these differences in electrical behavior are primarily due to differences in the potassium currents expressed in the two cell types. Ciliary neurons express a complement of potassium currents that are primarily geared towards the production of rapid repetitive firing. These include: (1) a small A-current; (2) a rapidly activating delayed rectifier; (3) voltage-and calcium-activated potassium channels that also participate in action potential repolarization; and (4) an inward rectifier that helps to repolarize the membrane. By contrast, sympathetic neurons express some potassium currents that inhibit repetitive firing: (1) a large A-current; (2) a slowly activating delayed rectifier; and (3) an M-current that reduces cellular excitability. / Other experiments show that divalent cations have a large effect on the voltage dependence of inactivation of the A-current without affecting any other voltage dependent parameter. The effects of divalent cations take place from outside the cell, a result that is not consistent with models of the inactivation process. These results suggest that these A-channels have a binding site for divalent cations on the external face of the channel. / Additional experiments show that in ciliary ganglion neurons, L-type Ca$\sp{2+}$ channels are preferentially coupled to I$\sb{\rm K\lbrack Ca\rbrack},$ although other Ca$\sp{2+}$ channel types are present. By contrast, in sympathetic neurons, N-type Ca$\sp{2+}$ and in some cases both types of Ca$\sp{2+}$ channels are functionally linked to I$\sb{\rm K\lbrack Ca\rbrack}.$ These results suggest that some neurons have the capacity to preferentially colocalize I$\sb{\rm K\lbrack Ca\rbrack}$ channels with specific Ca$\sp{2+}$ channel subtypes. The functional colocalization of Ca$\sp{2+}$ and I$\sb{\rm K\lbrack Ca\rbrack}$ channels may be an important regulatory mechanism in both developing and mature vertebrate neurons. / Source: Dissertation Abstracts International, Volume: 55-04, Section: B, page: 1321. / Major Professor: Stuart E. Dryer. / Thesis (Ph.D.)--The Florida State University, 1994.

Axonally transported proteoglycans were characterized in terms of their structure, subcellular localization, and possible functions during goldfish optic nerve regeneration. This study confirmed previous findings, that regeneration is correlated with an increase in the $\sp{35}$SO$\sb4$-radioactive labeling of the heparan sulfate and chondroitin sulfate glycosaminoglycan components of proteoglycans. Further, regenerating optic axons appear to transport proportionally more chondroitin sulfate than heparan sulfate, in contrast to intact axons, which favor heparan sulfate. The major change in glycosaminoglycan transport was seen at 21-28 days regeneration, a time of active axon growth and re-formation of synapses. Structural features of chondroitin sulfate, including molecular size, negative charge density, and sulfation site (carbon-4 of N-acetylgalactosamine), and the size of heparan sulfate do not change significantly during regeneration. In contrast, the heparan sulfate isolated from regenerating optic axons appears to have a lower negative charge density and altered sulfation pattern, indicating reduced sulfation. / The distribution of axonally transported proteoglycans among the soluble and membranous compartments of optic axons does not dramatically change with regeneration. However, increased proteoglycan radioactivity was found in each compartment, with the greatest increase in soluble locations. The in vivo findings suggest that the functions of axonally transported proteoglycans during goldfish optic nerve regeneration require increased amounts of chondroitin sulfate proteoglycans of types already present in the intact system, and heparan sulfate proteoglycans with an altered sulfation pattern. / Goldfish retinal explant cultures were used to observe the effects of different proteoglycan-perturbing treatments on retinal axon growth in vitro. Inhibition of proteoglycan synthesis and addition of a high concentration of heparan sulfate to the culture medium of explants reduced axon growth on a poly- scL-lysine substratum, while proteoglycan synthesis inhibition did not alter axon growth on poly- scL-lysine + laminin. This suggests that axonal proteoglycans facilitate outgrowth on poly- scL-lysine, while proteoglycan-laminin interactions are not necessary for regenerative outgrowth. Soluble chondroitin 4-sulfate stimulated axon growth on both substrata. Results support the hypothesis that proteoglycans participate in regenerative retinal axon outgrowth in the goldfish optic system. / Source: Dissertation Abstracts International, Volume: 55-04, Section: B, page: 1314. / Major Professor: John S. Elam. / Thesis (Ph.D.)--The Florida State University, 1994.

Two FMRFamide-like peptides, FMRFamide (Phe-Met-Arg-Phe-NH(,2)) and pQDPFLRFamide (pyroGlu-Asp-Pro-Phe-Leu-Arg-Phe-NH(,2)), were characterized and quantified from twenty three tissues of the snail, Helix aspersa. The peptides were widely but unevenly distributed in Helix, and were most concentrated in the central ganglia, male reproductive tract, posterior digestive system, tentacles and the blood. These peptides were localized in the peripheral tissues with immunocytochemical techniques. In all tissues, the peptides were observed exclusively in perikaria, nerves and nerve varocosities, and the density of staining was well correlated with the concentration measured by radioimmunoassay. Five select tissues, containing different concentrations of the endogenous peptides, were surveyed for their responses to FMRFamide, pQDPFLRFamide, acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). The responses to the peptides were distinguishable from those of ACh and 5-HT, and were diverse: excitatory effects were observed in the epiphallus and ventricle; biphasic effects were seen in the tentacle and pharyngeal retractor muscles; and inhibition occurred in the crop. Moreover, the responses to FMRFamide and pQDPFLRFamide peptide were not always the same. FMRFamide contracted the tentacle and pharyngeal retractor muscles whereas pQDPFLRFamide rarely had effects alone, but relaxed ACh and FMRFamide induced contractions. In Aplysia, FMRFamide was separated from SCP(,B) ("small cardioactive peptide", previously identified in Aplysia) by gel and ion-exchange chromatography, and was sequenced by sequential digestion with carboxypeptidase Y. Furthermore, FMRFamide and SCP(,B) have distinct biological actions, and their distribution amongst the central ganglia are different. / Source: Dissertation Abstracts International, Volume: 46-01, Section: B, page: 0073. / Thesis (Ph.D.)--The Florida State University, 1984.

The olfactory epithelium of vertebrates is known to contain a neurogenic matrix which serves for the replacement of the olfactory receptor neurons under normal or experimental circumstances. This matrix offers a unique opportunity for the study of neural proliferation and differentiation by providing a large homogenous population of developing neurons of a simple bipolar form. The present experiments investigate the ability of the neurogenic matrix to produce young neurons when removed from the nasal cavity and transplanted to the anterior chamber of the eye, and examine the differentiation of these neurons when deprived of both stimulation and appropriate target tissue. Transplants of postnatal olfactory mucosa and of the embryonic nasal pit have been observed with light and electron microscopy. / The matrix continues its production of new neurons for at least four months in oculo. The neurons extend their dendrites and axons, but only occasional receptors exhibiting fully differentiated characteristics (by ultrastructural and cytochemical criteria) are observed in both types of graft. The epithelium contained 50 to 60% of the normal complement of receptor elements, and twice as many mitoses and degenerations as found under normal circumstances. The scarcity of fully differentiated receptors and the frequent occurrence of degenerations indicates that the mature forms are short lived in the transplants, degenerating shortly after maturation. / Olfactory pit transplants consistently produced a convergence of olfactory axons from distant regions of the grafts, which was not observed in olfactory mucosa transplants. This indicates that the guidance mechanism directing the olfactory nerve to its normal target is intrinsic to the olfactory pit. Thus, attraction of the olfactory nerve to the brain by diffusable substances, or guidance along 'substrate pathways' between the nose and brain are not involved in this system. / After converging to form large aggregate bundles, the axons in pit grafts broke up to form a fiber plexus, resembling the fiber layer of the olfactory bulb, which contained isolated olfactory glomeruli. The formation of these glomeruli in the absence of target neurons proves that the signal initiating termination is a property of the olfactory axons, and does not rely on contact with postsynaptic dendrites. / Source: Dissertation Abstracts International, Volume: 47-07, Section: B, page: 2778. / Thesis (Ph.D.)--The Florida State University, 1986.

Chemosensory communication plays a major role in the reproductive physiology and behavior of several species. The vomeronasal organ, an "accessory olfactory" chemoreceptive structure, is thought to detect pheromonal signals from conspecifics. This system projects directly to central brain regions important in reproductive behavior. Removal of the vomeronasal organ, in sexually inexperienced male hamsters results in severe impairments of mating behavior and most animals do not mate. After sexual experience however, main olfactory pathways can sustain mating behavior in the absence of vomeronasal input. / The expression of an immediate early gene, c-fos was used as a marker of neuronal activation to distinguish the roles of chemosensory input in activating brain regions, important for mating. Activated brain and bulb regions were analyzed following mating or pheromonal stimulation in inexperienced and experienced male hamsters, both intact and those with vomeronasal organs removed. / Central vomeronasal pathways of inexperienced animals were activated above control levels after mating or pheromonal stimulation, while main olfactory pathways were not. Fos expression in the accessory olfactory bulb, posteromedial cortical amygdala and part of the medial nucleus, reflects activation by vomeronasal sensory input while activation in the caudal posteromedial bed nucleus of the stria terminalis (pmBNST) reflects chemoinvestigatory behavior. In inexperienced animals, the medial preoptic area (MPOA) and rostral pmBNST were activated only during copulatory performance but in sexually experienced males these regions were activated by both copulation and pheromonal stimulation. Fos expression patterns in experienced VNX animals may reflect rerouting of chemosensory information via main olfactory pathways and point to the anterior cortical nucleus, as an important region for this rerouting. / Behavioral data show that intracerebroventricular Luteinizing hormone releasing hormone (LHRH) injections can substantially restore mating behavior in inexperienced animals with vomeronasal organs removed. This action may be independent of the effects of LHRH on the pituitary. Fos and LHRH immunocytochemistry revealed an intermingling of LHRH cells and fibers with Fos activated neurons, consistent with the working hypothesis that intracerebral LHRH release may be involved in the mechanisms underlying vomeronasal chemoreception during mating behavior. / Source: Dissertation Abstracts International, Volume: 56-02, Section: B, page: 0669. / Major Professor: Michael Meredith. / Thesis (Ph.D.)--The Florida State University, 1994.

In human observers, prolonged viewing of a moving target causes a subsequently viewed stationary target to appear to move slowly in the opposite direction. Prolonged viewing also results in other motion aftereffects, including underestimates of the perceived velocity of subsequently viewed targets. These perceptual aftereffects are thought to be due to adaptation (the decrease in response following prolonged stimulation) of neurons in the visual cortex. The neural basis for motion perception was explored by studying the responses of single neurons in area 18 of the cat visual cortex to prolonged stimulus movement. The relationship between adaptation and velocity aftereffects was examined by comparing responses evoked by sinusoidal luminance gratings drifting at various rates before and after prolonged exposure to a grating drifting at a constant rate. / Virtually all neurons in area 18 exhibited adaptation. For most neurons, the time course of adaptation was described adequately by a simple exponential function. However, in a small number of neurons, the time course of adaptation was better described by a second-order equation like those used to model systems controlled by negative feedback. Exposure to rapidly drifting gratings resulted in more rapid and extensive adaptation than exposure to slowly drifting gratings. Neural aftereffects were bidirectional, and were most prominent at or above a neuron's preferred temporal frequency, regardless of the adapting temporal frequency. / The neuronal results were compared to velocity aftereffects, in which prolonged exposure to a moving target causes observers to underestimate the velocity of subsequently viewed targets. A vector-sum model was used to compute velocity based upon the pooled responses of neurons tuned to different temporal frequencies. When adaptation like that observed in area 18 neurons was incorporated into the model, the velocity of stimuli at or above the adapting velocity were underestimated, in agreement with human psychophysical data. This suggests that adaptation of visual cortical neurons may represent the substrate for velocity and other motion-related aftereffects. / Source: Dissertation Abstracts International, Volume: 52-08, Section: B, page: 4049. / Major Professor: Mark A. Berkley. / Thesis (Ph.D.)--The Florida State University, 1991.

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