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Prefrontal cortical modulation of posterior parietal acetylcholine release: a study of glutamatergic and cholinergic mechanisms

Nelson, Christopher L
http://rave.ohiolink.edu/etdc/view?acc_num=osu1069868437

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Neuroscience.
Attentional processing is a crucial early component of cognitive functions and capacities. The cognitive consequences of abnormal regulation of attentional processing are evident in neuropsychiatric diseases, including Alzheimers disease and schizophrenia, where subjects are characterized by attentional and cognitive impairments. Attention is subject to top-down regulation by areas of the cortex (prefrontal cortex [PFC]) associated with knowledge-driven and executive functions, leading to the processing of selected target stimuli, and filtering of others, for further cognitive processing. This top-down regulation involves modification of input processing in other cortical areas, such as the posterior parietal cortex (PPC). As cortical cholinergic inputs, originating from the basal forebrain cholinergic system (BFCS) have been demonstrated to mediate important aspects of attentional processing, and as these neurons are innervated by prefrontal outputs, a set of experiments investigated the pharmacological interactions between the BFCS and the PFC and PPC. Dual probe in vivo microdialysis was utilized for a series of experiments designed to demonstrate glutamatergic and cholinergic actions between the PFC and PPC, either through the BFCS and/or cortico-cortical interactions. The first set of experiments demonstrated a uni-directional increase in PFC and PPC acetylcholine (ACh) efflux following AMPA administration to the PFC, antagonized by co-administration of the AMPA receptor antagonist DNQX. The second set of experiments demonstrated that nicotine and the mixed cholinergic agonist carbachol both produced increases in local (PFC) ACh efflux, but only carbachol increased PPC ACh efflux. This PPC effect of carbachol was uni-directional, and attenuated by co-administration of a muscarinic antagonist (atropine), and also moderately attenuated by DNQX and the nicotinic antagonist mecamylamine. Collectively, these studies demonstrate the capacity of the PFC to regulate ACh efflux in distal cortical areas (PPC) via glutamatergic and cholinergic mechanisms, and that this is a uni-directional effect. These studies begin to elucidate neurochemical mechanisms underlying the top-down regulation of attentional functions, and will contribute to an understanding of the consequences of PFC dysfunction on attentional processing. Attentional processing is a crucial early component of cognitive functions and capacities. The cognitive consequences of abnormal regulation of attentional processing are evident in neuropsychiatric diseases, including Alzheimers disease and schizophrenia, where subjects are characterized by attentional and cognitive impairments. Attention is subject to top-down regulation by areas of the cortex (prefrontal cortex [PFC]) associated with knowledge-driven and executive functions, leading to the processing of selected target stimuli, and filtering of others, for further cognitive processing. This top-down regulation involves modification of input processing in other cortical areas, such as the posterior parietal cortex (PPC). As cortical cholinergic inputs, originating from the basal forebrain cholinergic system (BFCS) have been demonstrated to mediate important aspects of attentional processing, and as these neurons are innervated by prefrontal outputs, a set of experiments investigated the pharmacological interactions between the BFCS and the PFC and PPC. Dual probe in vivo microdialysis was utilized for a series of experiments designed to demonstrate glutamatergic and cholinergic actions between the PFC and PPC, either through the BFCS and/or cortico-cortical interactions. The first set of experiments demonstrated a uni-directional increase in PFC and PPC acetylcholine (ACh) efflux following AMPA administration to the PFC, antagonized by co-administration of the AMPA receptor antagonist DNQX. The second set of experiments demonstrated that nicotine and the mixed cholinergic agonist carbachol both produced increases in local (PFC) ACh efflux, but only carbachol increased PPC ACh efflux. This PPC effect of carbachol was uni-directional, and attenuated by co-administration of a muscarinic antagonist (atropine), and also moderately attenuated by DNQX and the nicotinic antagonist mecamylamine. Collectively, these studies demonstrate the capacity of the PFC to regulate ACh efflux in distal cortical areas (PPC) via glutamatergic and cholinergic mechanisms, and that this is a uni-directional effect. These studies begin to elucidate neurochemical mechanisms underlying the top-down regulation of attentional functions, and will contribute to an understanding of the consequences of PFC dysfunction on attentional processing.
John Bruno (Advisor)
130 p.
Biology, Neuroscience
acetylcholine; attention; glutamate; microdialysis; prefrontal cortex; basal forebrain; posterior parietal cortex

Recommended Citations

Citations

  • Nelson, C. L. (2004). Prefrontal cortical modulation of posterior parietal acetylcholine release: a study of glutamatergic and cholinergic mechanisms [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1069868437

    APA Style (7th edition)

  • Nelson, Christopher. Prefrontal cortical modulation of posterior parietal acetylcholine release: a study of glutamatergic and cholinergic mechanisms. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1069868437.

    MLA Style (8th edition)

  • Nelson, Christopher. "Prefrontal cortical modulation of posterior parietal acetylcholine release: a study of glutamatergic and cholinergic mechanisms." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1069868437

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.