Present knowledge indicates the importance of one region of monkey temporal association cortex, the superior temporal sulcus (STS), in predominantly high level analysis of 'biologically' important objects. To clarify and elaborate on the function of the monkey STS, the following questions are addressed: (1) what kind of tactile processing occurs in the polymodal STS and does it compare with the complex visual processing observed; (2) does behavioural sensitivity to face and body information parallel neural sensitivity (of STS cells) to the same stimulus dimensions; (3) does monkey STS ablation result in a behavioural indication of impairments in the perception of socially relevant stimuli; and (4) are visual cells in the STS sensitive to social communicational elements of facial or postural expression? Single-unit recording studies of the macaque STS (using standard techniques in awake, behaving animals) reveal a population of somatosensory neurones, with large receptive fields, sensitive only to unexpected (unpredictable) tactile stimulation. Complex tactual-visual interactions observed stress the importance of this dimension of processing. A separate population of visual cells exhibit sensitivity to compound facial expressions and head/body postures important in primate social communication. A behavioural study of monkeys' socio-emotional responses to configurational aspects of faces, the posture of the head and the interaction of form and motion, reveal their ability to discriminate salient cues in the context of social communication/interaction. It is tentatively shown that monkeys with the STS ablated are unable to make such discriminations, so reacting inappropriately to the stimuli (a symptom of Kluver-Bucy syndrome). The combined findings show that the STS performs a multimodal perceptual analysis of socially relevant stimuli, and suggest that the STS provides a sensory input to a limbic structure, such as the amygdala, through which it mediates appropriate emotional reactive behaviour.

1. Electrical characteristics of the cell body of an identified motoneurone, the 'fast' coxal depressor motoneurone (Df), from the cockroach (Periplaneta americana) have been studied under current- and voltage-clamp. 2. In response to low magnitude, relatively long duration depolarising current pulses, Df could generate plateau potentials, regenerative events which often far outlived the duration of the applied depolarisation. 3. Plateau potentials constitute an inherent property of the neurone because they could be evoked in somata that had been surgically isolated from other parts of the neurone (the soma is devoid of synaptic contacts); these experiments also demonstrated that the soma of this neurone can participate in the generation of plateau potentials. 4. Plateau potentials were often surmounted by attenuated action potentials; these correlated 1:1 with axonal impulses recorded extracellularly from the axon of the neuron. 5. Plateau potentials were associated with an increase in membrane conductance. Under voltage- clamp, cells which exhibited plateau potentials possessed a region of negative slope resistance in their current-voltage relationship. 6. Plateau potentials in Df were observed to be calcium-dependent, A series of current- and voltage- damp experiments indicated that the calcium channels involved in plateau potential production differ from those which can mediate calcium-dependent action potentials following pharmacological treatment of this neurone. 7. Plateau potential production in Df was suppressed by the application of GABA (10-4M). Spontaneous plateau potentials could be recorded following application of picrotoxin (10-5M) or pentylenetetrazole (25mM). 8. Recordings taken from two other 'fast' motoneurones, cell 3 (from the cockroach) and FETi (from the locust, Schistocerca gregaria) indicated that the ability to generate plateau potentials may not be restricted to Df. 9. Although freshly dissected, recently impaled neurones responded to relatively brief depolarising current pulses with a series of graded, damped membrane oscillations, the excitability of many preparations increased with time from dissection: many cells became able to generate all-or-none action potentials in response to such pulses (these differed from the attenuated axonal spikes which often surmounted plateau potentials). The appearance of these events did not correlate with consistent changes to the resting potential or input resistance of neurones. 10. Time-dependent action potentials were calcium-dependent and could be recorded from 'intact' cells and isolated neurone somata. These action potentials could also co-exist with plateau potentials; such co-existence provides evidence for different classes of calcium channel in untreated insect neurones.

Oxysterols are oxygenated derivatives of cholesterol or its precursors. One oxysterol, 24(S),25-epoxycholesterol (24(S),25-EC), which results from a shunt in the cholesterol synthesis pathway has been found at higher than expected levels in embryonic murine brain. Interestingly, the receptor that 24(5),25-EC is a ligand for, Liver X Receptor (LXR), has been implicated in neurogenesis in the ventral mid brain region of embryonic brain; an area with a high density of dopaminergic neurons. The mechanism by which LXR induces this effect is unclear. Therefore, proteomic and phosphoproteomic studies were performed using a stable isotope labelled in amino acid in cell culture (SILAC) approach in order to quantify changes in the proteome between different treatment groups in a mouse substantia nigra dopaminergic cell line (SN4741) SN4741 cells were cultured in SILAC media containing differentially isotope labelled arginine and lysine. For protein expression studies SN4741 cells were treated in serum free media with vehicle, 10muM 24(S),25-EC, or 1muM GW3965, a synthetic ligand of LXR, for 24 hours. For analysis of changes in the phosphoproteome SN4741 cells were treated in serum free media with vehicle, 10muM 24(5),25-EC, or 30muM 25- hydroxycholesterol for 6 hours. Cells were lysed and protein combined in a 1:1 ratio before trypsin digestion and peptide separation via strong cation exchange chromatography. Phosphopeptides were enriched using immobilised metal affinity chromatography (IMAC). Resulting fractions were analysed, using a data dependent LC-MS/MS method. Data was quantified using MaxQuant software in conjunction with Mascot using an IPl mouse database. In protein expression analysis known oxysterol regulated genes, via SREBP or LXR, were differentially expressed. Oxysterol treatment induced global changes in proteins involved in lipid (cholesterol, fatty acid, phospholipid, triglyceride) synthesis. LXR? protein expression increased after GW3965 and 24(5),25-EC treatment, though no change was seen on LXRp mRNA, implying that ligand binding protects LXR? from degradation. 24(S),25-EC induced changes in expression and localisation of the membrane protein caveolin-1. Also, phosphoethanolamine cytidylyltransferase and collagen type IV alpha-3-binding protein, 2 proteins involved in phospholipid synthesis, had an altered expression after 24(S),25-EC treatment suggesting a role for oxysterols in membrane homeostasis. A cytokine, macrophage colony stimulating factor, which is required for normal neuronal development and macrophage differentiation had an LXR independent increased expression after 24(S),25-EC treatment. Quantitative RT-PCR data demonstrated that proteomic changes were due to both transcriptional and post-transcriptional effects of oxysterol. In addition, studies examining changes in the mouse phosphoproteome identified a number of novel phosphorylation sites.

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The primary auditory cortex (area AI) plays an important role in the localization of static sound sources. However, little is known concerning how it processes information about sound source motion. This study was undertaken to investigate the responses of single neurons in the primary auditory cortex of the cat to correlates of auditory motion in space. Diotic and dichotic changes in sound intensity presented through earphones simulated auditory motion in four directions: toward and away from the receiver along the midline, into the ipsilateral hemifield and into the contralateral hemifield. Different rates of intensity change simulated sound source velocity. Results indicate that AI neurons can be highly selective to intensity correlates of auditory motion. Three major classes of neurons were encountered: neurons sensitive to motion toward or away from the receiver, neurons sensitive to ipsilateral- or contralateral-directed motion, and monaural-like neurons. The different classes of direction-selective neurons were spatially segregated from each other and appeared to occur in clusters or columns in the cortex. In addition to their selectivity for different directions of simulated sound source motion, AI neurons also responded selectively to the rate and excursion of intensity changes, a correlate of sound source velocity. The major determinants of direction and velocity selectivity were interactions between the following response properties of AI neurons: binaural interaction type, ear dominance, on/off responses, and monotonicity of rate/intensity function. These findings suggest that neural processing of auditory motion may involve neural mechanisms distinct from those involved in static sound localization, and indicate that some neurons in the primary auditory cortex may be part of a specialized motion-detecting mechanism in the auditory system. / Arts, Faculty of / Psychology, Department of / Graduate

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Psychology, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND HUMANITIES / Bibliography: leaves 36-40. / by Douglas Allen Whittington. / Ph.D.

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The role of L-Lactate has expanded from an energy metabolite to a signaling molecule in neurons. Studies have shown that L-Lactate plays a role in neuroprotection and in NMDAR-dependent long-term memory formation. The aim of this dissertation is to characterize the role of L-Lactate as a signaling molecule and understand the molecular mechanism through which L-Lactate potentiates NMDAR signal. Using mass spectrometry, I monitored the time-dependent changes in the phosphoproteome of cortical neuronal cultures in response to Lactate. The phosphoproteomic analysis highlighted a number of cytoskeletal proteins involved in synapse remodeling as well as axon guidance that were regulated by L-Lactate. In addition, I found that L-Lactate induced phosphorylation of proteins involved in the MAPK pathway, as reported in an earlier study. I hypothesize the involvement of CaMKII in this mechanism. CaMKII is one of the most abundant kinases in the brain and plays a role in learning and memory via interaction with NMDAR. Using CaMKII inhibitors and mutants of the NMDAR subunit GluN2B, the findings in this dissertation provide evidence for the involvement of CaMKII, specifically, the interaction between CaMKIIa and GluN2B, as a requirement for the L-Lactate mediated potentiation of NMDAR signal. In addition, to gain insight into the evolution of lactate from a metabolite to a signaling molecule, this study explores the evolution of glutamate as a signaling molecule in multicellular organisms so it may serve as a model for evolution of metabolites like lactate into signaling molecules. For this purpose, the model organism Hydra was used, since it belongs to phylum Cnidaria, evolutionarily one of the first phyla to have a nervous system. In order to explore whether glutamate receptors, particularly, NMDAR are functionally expressed in Hydra and are localized in neurons, a line of transgenic Hydra expressing a calcium indicator (GCaMP6s) in neurons was generated. With the transgenic Hydra line, I attempted to measure the in vivo response of neurons in Hydra to glutamate. This study highlights several ground work experiments with an extensive discussion of implications and challenges and an outlook for future investigations.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

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