Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels

S M Cochran, A L Harvey, J A Pratt

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Abstract

The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.
LanguageEnglish
Pages1455-1463
Number of pages9
JournalEuropean Journal of Neuroscience
Volume14
Issue number9
DOIs
Publication statusPublished - Nov 2001

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Charybdotoxin
Glucose
Brain
Hippocampus
Deoxyglucose
Seizures
Learning

Keywords

  • animals
  • basal ganglia
  • brain
  • carbon radioisotopes
  • cerebral cortex
  • charybdotoxin
  • dentate gyrus
  • deoxyglucose
  • energy metabolism
  • glucose
  • hippocampus
  • limbic system
  • male
  • memory
  • neural pathways
  • neurons
  • potassium channels
  • rats
  • septal nuclei
  • voltage-gated
  • long-evans

Cite this

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title = "Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels",
abstract = "The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.",
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author = "Cochran, {S M} and Harvey, {A L} and Pratt, {J A}",
year = "2001",
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TY - JOUR

T1 - Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels

AU - Cochran, S M

AU - Harvey, A L

AU - Pratt, J A

PY - 2001/11

Y1 - 2001/11

N2 - The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.

AB - The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.

KW - animals

KW - basal ganglia

KW - brain

KW - carbon radioisotopes

KW - cerebral cortex

KW - charybdotoxin

KW - dentate gyrus

KW - deoxyglucose

KW - energy metabolism

KW - glucose

KW - hippocampus

KW - limbic system

KW - male

KW - memory

KW - neural pathways

KW - neurons

KW - potassium channels

KW - rats

KW - septal nuclei

KW - voltage-gated

KW - long-evans

U2 - 10.1046/j.0953-816x.2001.01770.x

DO - 10.1046/j.0953-816x.2001.01770.x

M3 - Article

VL - 14

SP - 1455

EP - 1463

JO - European Journal of Neuroscience

T2 - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 9

ER -