Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat
Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. Medicine Bibliography: leaves 78-89 Exogenous norepinephrine (NE) potentiates the evoked potential (EP) recorded from the dentate gyrus (DG) of the hippocampus in vivo (Neuman and Harley, 1983; Winson and Dahl, 1985) and in vitro (Lacaille a...
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2002
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Online Access: | http://collections.mun.ca/cdm/ref/collection/theses3/id/198154 |
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institution |
Open Polar |
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Memorial University of Newfoundland: Digital Archives Initiative (DAI) |
op_collection_id |
ftmemorialunivdc |
language |
English |
topic |
Dentate gyrus--Physiology Cognitive learning--Physiological aspects;Memory--Physiological aspects Learning--physiology Memory--physiology |
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Dentate gyrus--Physiology Cognitive learning--Physiological aspects;Memory--Physiological aspects Learning--physiology Memory--physiology Knight, John Christopher, 1970- Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
topic_facet |
Dentate gyrus--Physiology Cognitive learning--Physiological aspects;Memory--Physiological aspects Learning--physiology Memory--physiology |
description |
Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. Medicine Bibliography: leaves 78-89 Exogenous norepinephrine (NE) potentiates the evoked potential (EP) recorded from the dentate gyrus (DG) of the hippocampus in vivo (Neuman and Harley, 1983; Winson and Dahl, 1985) and in vitro (Lacaille and Harley, 1985; Stanton and Sarvey, 1985b). Endogenous NE released by activation of the locus coeruleus (LC) system by glutamatergic (Harley and Milway, 1986; Harley and Evans, 1988) or electrical stimulation (Dahl and Winson, 1985, Assaf et al., 1979; Washburn and Moises, 1989) of the LC or its input, the nucleus paragigantocellularis (Babstock and Harley, 1992) has similar effects. Evidence suggests that the initiation of these potentiations are mediated by β-adrenergic activation and that local β-receptors in the DG play an important role in this phenomenon (Lacaille and Harley, 1985; Stanton and Sarvey, 1985b; Babstock and Harley, 1992; Washburn and Moises, 1989; Harley and Milway, 1986). NE has also been shown to excite and inhibit interneurons recorded in the DG (Rose and Pang, 1989; Clarke 1995). -- Yet another method of releasing endogenous LC-NE and subsequent potentiation of the DG EP is via systemic application of the α2-antagonist idazoxan (IDA) (Cedarbaum and Aghajanian, 1978; Richter-Levin, 1991; Sara and Bergis, 1991). IDA has also been shown to result in an increase in paired-pulse inhibition in the DG (Sara and Bergis, 1991). -- The present study utilized the paired-pulse paradigm and double pipette technique to examine the role of β-receptor activation in IDA-induced NE modulation of excitation and inhibition in the local circuitry of the DG. Saline and timolol-filled micropipettes were placed in the DG of urethane-anaesthetized rats. The perforant path was stimulated with paired pulses spaced at short intervals and rats were given systemic injection of IDA after baseline recroding. Evidence was demonstrated for five distinct effects of NE in the local circuitry of the DG. These were: 1) enhancement of tonic activity of somatic inhibitory interneurons at baseline via low threshold p-receptor activation; 2) increased cell firing to a constant input supported by a high-threshold direct p-receptor action on granule cell membranes; 3) a decrease in EPSP size probably due to increased feed-forward dendritic inhibition; 4) inhibition of somatic feedback disinhibition circuits (rather than an increase in inhibition per se); and 5) enhancement of firing of feedback dendritic inhibitory interneurons possibly via α1 -receptor activation. Effects observed in the DG with IDA in the present study were compared to those observed during learning and exploration of a new environment in other studies. |
author2 |
Memorial University of Newfoundland. Faculty of Medicine |
format |
Thesis |
author |
Knight, John Christopher, 1970- |
author_facet |
Knight, John Christopher, 1970- |
author_sort |
Knight, John Christopher, 1970- |
title |
Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
title_short |
Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
title_full |
Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
title_fullStr |
Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
title_full_unstemmed |
Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
title_sort |
pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat |
publishDate |
2002 |
url |
http://collections.mun.ca/cdm/ref/collection/theses3/id/198154 |
long_lat |
ENVELOPE(170.483,170.483,-83.583,-83.583) ENVELOPE(43.352,43.352,66.332,66.332) ENVELOPE(-128.689,-128.689,69.800,69.800) ENVELOPE(-86.133,-86.133,-77.617,-77.617) |
geographic |
Ida Levin Stanton Washburn |
geographic_facet |
Ida Levin Stanton Washburn |
genre |
Newfoundland studies University of Newfoundland |
genre_facet |
Newfoundland studies University of Newfoundland |
op_source |
Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries |
op_relation |
Electronic Theses and Dissertations (9.91 MB) -- http://collections.mun.ca/PDFs/theses/Knight_JohnChristopher.pdf a1562139 http://collections.mun.ca/cdm/ref/collection/theses3/id/198154 |
op_rights |
The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. |
_version_ |
1766113191520108544 |
spelling |
ftmemorialunivdc:oai:collections.mun.ca:theses3/198154 2023-05-15T17:23:33+02:00 Pharmacological evaluation of idazoxan-induced noradrenergic modulation of excitatory and inhibitory processes in the dentate gyrus of the anaesthetized rat Knight, John Christopher, 1970- Memorial University of Newfoundland. Faculty of Medicine 2002 ix, 89 leaves : ill. Image/jpeg; Application/pdf http://collections.mun.ca/cdm/ref/collection/theses3/id/198154 eng eng Electronic Theses and Dissertations (9.91 MB) -- http://collections.mun.ca/PDFs/theses/Knight_JohnChristopher.pdf a1562139 http://collections.mun.ca/cdm/ref/collection/theses3/id/198154 The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Paper copy kept in the Centre for Newfoundland Studies, Memorial University Libraries Dentate gyrus--Physiology Cognitive learning--Physiological aspects;Memory--Physiological aspects Learning--physiology Memory--physiology Text Electronic thesis or dissertation 2002 ftmemorialunivdc 2015-08-06T19:20:53Z Thesis (M.Sc.)--Memorial University of Newfoundland, 2002. Medicine Bibliography: leaves 78-89 Exogenous norepinephrine (NE) potentiates the evoked potential (EP) recorded from the dentate gyrus (DG) of the hippocampus in vivo (Neuman and Harley, 1983; Winson and Dahl, 1985) and in vitro (Lacaille and Harley, 1985; Stanton and Sarvey, 1985b). Endogenous NE released by activation of the locus coeruleus (LC) system by glutamatergic (Harley and Milway, 1986; Harley and Evans, 1988) or electrical stimulation (Dahl and Winson, 1985, Assaf et al., 1979; Washburn and Moises, 1989) of the LC or its input, the nucleus paragigantocellularis (Babstock and Harley, 1992) has similar effects. Evidence suggests that the initiation of these potentiations are mediated by β-adrenergic activation and that local β-receptors in the DG play an important role in this phenomenon (Lacaille and Harley, 1985; Stanton and Sarvey, 1985b; Babstock and Harley, 1992; Washburn and Moises, 1989; Harley and Milway, 1986). NE has also been shown to excite and inhibit interneurons recorded in the DG (Rose and Pang, 1989; Clarke 1995). -- Yet another method of releasing endogenous LC-NE and subsequent potentiation of the DG EP is via systemic application of the α2-antagonist idazoxan (IDA) (Cedarbaum and Aghajanian, 1978; Richter-Levin, 1991; Sara and Bergis, 1991). IDA has also been shown to result in an increase in paired-pulse inhibition in the DG (Sara and Bergis, 1991). -- The present study utilized the paired-pulse paradigm and double pipette technique to examine the role of β-receptor activation in IDA-induced NE modulation of excitation and inhibition in the local circuitry of the DG. Saline and timolol-filled micropipettes were placed in the DG of urethane-anaesthetized rats. The perforant path was stimulated with paired pulses spaced at short intervals and rats were given systemic injection of IDA after baseline recroding. Evidence was demonstrated for five distinct effects of NE in the local circuitry of the DG. These were: 1) enhancement of tonic activity of somatic inhibitory interneurons at baseline via low threshold p-receptor activation; 2) increased cell firing to a constant input supported by a high-threshold direct p-receptor action on granule cell membranes; 3) a decrease in EPSP size probably due to increased feed-forward dendritic inhibition; 4) inhibition of somatic feedback disinhibition circuits (rather than an increase in inhibition per se); and 5) enhancement of firing of feedback dendritic inhibitory interneurons possibly via α1 -receptor activation. Effects observed in the DG with IDA in the present study were compared to those observed during learning and exploration of a new environment in other studies. Thesis Newfoundland studies University of Newfoundland Memorial University of Newfoundland: Digital Archives Initiative (DAI) Ida ENVELOPE(170.483,170.483,-83.583,-83.583) Levin ENVELOPE(43.352,43.352,66.332,66.332) Stanton ENVELOPE(-128.689,-128.689,69.800,69.800) Washburn ENVELOPE(-86.133,-86.133,-77.617,-77.617) |