Hyperexcitability of distal dendrites in hippocampal pyramidal cells after chronic partial deafferentation.
Traumatic injury to the CNS results in chronic partial deafferentation of subsets of surviving neurons. Such injuries are often followed by a delayed but long-lasting period of aberrant hyperexcitability. The cellular mechanisms underlying this delayed hyperexcitability are poorly understood. We developed an in vitro model of deafferentation and reactive hyperexcitability using organotypic hippocampal slice cultures to study the underlying cellular mechanisms. One week after transection of the Schaffer collateral and temporoammonic afferents to CA1 neurons, brief tetanic stimulation of the residual excitatory synapses produced abnormally prolonged depolarizations, compared with responses in normally innervated neurons. Responses to weak stimulation, in contrast, were unaffected after deafferentation. Direct stimulation of distal apical dendrites using focal photolysis of caged glutamate triggered abnormally prolonged plateau potentials in the deafferented neurons when strong stimulation was given, but responses to weak stimulation were not different from controls. An identical phenotype was produced by chronic "chemical deafferentation" with glutamate receptor antagonists. Responses to strong synaptic and photolytic stimulation were selectively prolonged by small-conductance (SK-type) calcium-activated potassium channel blockers in normally innervated cells but not after deafferentation. No significant changes in SK2 mRNA or protein levels, GABAergic inhibition, glutamate receptor function, input resistance, or action potential parameters were observed after chronic deafferentation. We suggest that a posttranslational downregulation of SK channel function in thin distal dendrites is a significant contributor to deafferentation-induced reactive hyperexcitability.
Cai
Xiang
X
Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Wei
Dong-Sheng
DS
Gallagher
Sandra E
SE
Bagal
Ashish
A
Mei
Yan-Ai
YA
Kao
Joseph P Y
JP
Thompson
Scott M
SM
Tang
Cha-Min
CM
D000200:Action Potentials / Q000502:physiology*; D000344:Afferent Pathways / Q000166:cytology / Q000502:physiology*; D000818:Animals; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats