Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.
Focal cortical injuries result in death of cortical neurons and their efferents and ultimately in death or damage of thalamocortical relay (TCR) neurons that project to the affected cortical area. Neurons of the inhibitory reticular thalamic nucleus (nRT) receive excitatory inputs from corticothalamic and thalamocortical axons and are thus denervated by such injuries, yet nRT cells generally survive these insults to a greater degree than TCR cells. nRT cells inhibit TCR cells, regulate thalamocortical transmission, and generate cerebral rhythms including those involved in thalamocortical epilepsies. The survival and reorganization of nRT after cortical injury would determine recovery of thalamocortical circuits after injury. However, the physiological properties and connectivity of the survivors remain unknown. To study possible alterations in nRT neurons, we used the rat photothrombosis model of cortical stroke. Using in vitro patch-clamp recordings at various times after the photothrombotic injury, we show that localized strokes in the somatosensory cortex induce long-term reductions in intrinsic excitability and evoked synaptic excitation of nRT cells by the end of the first week after the injury. We find that nRT neurons in injured rats show (1) decreased membrane input resistance, (2) reduced low-threshold calcium burst responses, and (3) weaker evoked excitatory synaptic responses. Such alterations in nRT cellular excitability could lead to loss of nRT-mediated inhibition in relay nuclei, increased output of surviving TCR cells, and enhanced thalamocortical excitation, which may facilitate recovery of thalamic and cortical sensory circuits. In addition, such changes could be maladaptive, leading to injury-induced epilepsy.
Paz
Jeanne T
JT
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Christian
Catherine A
CA
Parada
Isabel
I
Prince
David A
DA
Huguenard
John R
JR
D000818:Animals; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D017097:Electric Impedance; D005071:Evoked Potentials; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000503:physiopathology; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013787:Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
D020747:Calcium Channels, T-Type; D002118:Calcium
J Neurosci. 2000 Jul 15;20(14):5264-75
10884310
J Neurophysiol. 1993 Jul;70(1):158-66
8395572
Synapse. 2005 Mar 1;55(3):176-82
15635696
J Neurophysiol. 2006 May;95(5):3073-85
16617177
J Neurosci. 2006 Aug 16;26(33):8633-45
16914689
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
J Neurosci. 1992 Oct;12(10):3804-17
1403085
Epilepsy Res. 2003 Oct;56(2-3):185-203
14643003
J Physiol. 1995 Mar 15;483 ( Pt 3):665-85
7776250
Eur J Neurosci. 2006 Nov;24(9):2581-94
17100846
Nature. 1982 Jun 3;297(5865):406-8
7078650
Annu Rev Physiol. 1996;58:299-327
8815797
Int J Dev Neurosci. 1993 Apr;11(2):157-74
7687085
Pflugers Arch. 2004 May;448(2):131-8
14770314
J Physiol. 1993 Oct;470:273-94
8308730
Stroke. 1990 May;21(5):790-4
1692645
J Neurophysiol. 2003 Jan;89(1):177-85
12522170
Nature. 1996 Aug 29;382(6594):807-10
8752273
J Comp Neurol. 1965 Dec;125(3):329-36
15101318
Pharmacol Rev. 1999 Mar;51(1):7-61
10049997
J Cereb Blood Flow Metab. 1992 Nov;12(6):954-61
1400649
J Comp Neurol. 1998 Mar 9;392(2):252-63
9512272
J Neurosci. 1986 Aug;6(8):2134-45
3746404
J Physiol. 2006 Jul 15;574(Pt 2):415-30
16644797
Trends Neurosci. 2005 Jun;28(6):317-24
15927688
J Neurosci. 1994 Sep;14(9):5485-502
8083749
J Neurosci. 2009 Sep 30;29(39):12059-69
19793964
Ann Neurol. 1985 May;17(5):497-504
4004172
Neuroscience. 1988 Nov;27(2):629-38
3217007
Epilepsy Res. 2001 Dec;47(3):189-203
11738927
FEBS Lett. 2002 Sep 25;528(1-3):272-8
12297319
J Physiol. 1978 Jun;279:167-85
566793
Neuroscience. 2006 Sep 15;141(4):1811-25
16806719
Nat Neurosci. 1998 Sep;1(5):389-94
10196529
Annu Rev Physiol. 2002;64:355-405
11826273
Curr Opin Cell Biol. 1994 Feb;6(1):34-40
7513179
Brain Res. 1996 Sep 23;734(1-2):1-9
8896802
Folia Neuropathol. 1998;36(1):7-14
9595858
Nat Rev Neurosci. 2003 Dec;4(12):957-67
14618155
J Neurosci. 1999 Mar 15;19(6):1912-21
10066244
Neuropsychopharmacology. 2004 Jul;29(7):1353-62
15054476
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6303-7
8022776
Neurology. 1996 Feb;46(2):350-5
8614493
J Neurosci Methods. 1991 Apr;37(2):121-31
1908929
J Neurocytol. 1973 Sep;2(3):265-88
9224491
Science. 1999 Jan 22;283(5401):541-3
9915702
J Neurosci Methods. 1988 Aug;25(1):1-11
3146670
J Physiol. 1989 Sep;416:111-22
2558172
J Neurosci. 1997 Jan 1;17(1):277-95
8987755
J Physiol. 2009 Sep 1;587(Pt 17):4213-33
19564397
Neuroscience. 1990;35(3):525-50
2166245
Brain. 1965 Sep;88(3):539-56
5318823
Acta Neuropathol. 1987;72(4):315-25
3577687
J Neurophysiol. 1993 Dec;70(6):2354-69
8120587
J Physiol. 2003 Nov 1;552(Pt 3):881-905
12923213
J Cereb Blood Flow Metab. 2002 Dec;22(12):1463-75
12468891
J Physiol. 1993 Aug;468:669-91
8254530
Physiol Rev. 2003 Jan;83(1):117-61
12506128
J Biol Chem. 2001 Feb 9;276(6):3999-4011
11073957
J Neurosci. 2007 Jan 24;27(4):929-41
17251435
J Neurosci. 2002 Mar 15;22(6):2323-34
11896171
J Anat. 1953 Oct;87(4):387-406
13117757
Exp Brain Res. 1996 Nov;112(2):203-12
8951389
J Cereb Blood Flow Metab. 1996 Sep;16(5):906-14
8784234