Timing and location of synaptic inputs determine modes of subthreshold integration in striatal medium spiny neurons.
Medium spiny neurons (MSNs) are the principal cells of the striatum and perform a central role in sensorimotor processing. MSNs must integrate many excitatory inputs located across their dendrites to fire action potentials and enable striatal function. However, the dependence of synaptic responses on the temporal and spatial distribution of these inputs remains unknown. Here, we use whole-cell recordings, two-photon microscopy, and two-photon glutamate uncaging to examine subthreshold synaptic integration in MSNs from acute rat brain slices. We find that synaptic responses can summate sublinearly, linearly, or supralinearly depending on the spatiotemporal pattern of activity. Repetitive activity at single inputs leads to sublinear summation, reflecting long-lived AMPA receptor desensitization. In contrast, asynchronous activity at multiple inputs generates linear summation, with synapses on neighboring spines functioning independently. Finally, synchronous activity at multiple inputs triggers supralinear summation at depolarized potentials, reflecting activation of NMDA receptors and L-type calcium channels. Thus, the properties of subthreshold integration in MSNs are determined by the distribution of synaptic inputs and the differential activation of multiple postsynaptic conductances.
Carter
Adam G
AG
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Soler-Llavina
Gilberto J
GJ
Sabatini
Bernardo L
BL
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology*; D049229:Dendritic Spines / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000145:classification / Q000502:physiology*; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D002118:Calcium
Neuron. 1999 Feb;22(2):383-94
10069343
Neuron. 1999 Feb;22(2):395-409
10069344
Neuroscience. 1999 Jan;88(2):479-88
10197768
Nature. 1999 May 13;399(6732):151-5
10335844
Nature. 2000 Mar 16;404(6775):285-9
10749211
J Neurophysiol. 2000 Jun;83(6):3310-22
10848551
Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1255-60
11158626
Science. 2001 Sep 21;293(5538):2272-5
11567143
J Neurosci. 2001 Oct 15;21(20):8062-71
11588179
Neuron. 2001 Oct 25;32(2):301-13
11683999
J Neurophysiol. 2002 Jan;87(1):157-65
11784738
J Neurophysiol. 2002 Feb;87(2):1007-17
11826064
J Neurosci. 2002 Feb 1;22(3):740-7
11826103
Neuron. 2002 Jan 31;33(3):439-52
11832230
Neuron. 2002 Feb 28;33(5):779-88
11879654
Nat Neurosci. 2002 Jul;5(7):657-64
12055631
Eur J Neurosci. 1992;4(10):929-935
12106428
Neuron. 2002 Dec 19;36(6):1115-26
12495626
J Neurosci. 2003 Mar 15;23(6):2182-92
12657677
Biomed Eng Online. 2003 May 17;2:13
12801419
J Neurosci. 2003 Jun 15;23(12):4868-77
12832509
J Physiol. 2003 Nov 15;553(Pt 1):169-82
12963790
J Physiol. 1992 Dec;458:409-23
1302270
J Neurosci. 1992 Nov;12(11):4224-33
1359031
Neuron. 1992 Nov;9(5):991-9
1384578
Nat Neurosci. 2004 Jun;7(6):621-7
15156147
Neuron. 2004 Oct 14;44(2):351-64
15473972
Neuron. 2004 Oct 28;44(3):483-93
15504328
J Neurosci. 2005 Feb 2;25(5):1050-62
15689540
J Neurosci. 2005 Nov 9;25(45):10537-45
16280591
J Neurosci. 2006 Feb 15;26(7):2088-100
16481442
Neuron. 2006 Apr 20;50(2):291-307
16630839
J Comp Neurol. 2006 Nov 1;499(1):33-48
16958106
J Physiol. 2007 Apr 1;580(Pt 1):225-40
17234703
Nature. 2007 Feb 8;445(7128):643-7
17287809
J Neurosci. 2007 May 16;27(20):5448-60
17507567
J Neurophysiol. 1990 Apr;63(4):663-75
2341867
J Neurophysiol. 1989 Nov;62(5):1052-68
2585039
Brain Res. 1988 Nov 8;473(1):187-92
2850087
Neurosci Lett. 1995 Jun 16;192(3):213-7
7566653
Neuron. 1995 Nov;15(5):1097-107
7576653
J Neurosci. 1993 Aug;13(8):3496-509
7688040
J Neurosci. 1995 May;15(5 Pt 1):3622-39
7751934
J Neurosci. 1994 Aug;14(8):4871-81
8046457
J Neurophysiol. 1994 Jan;71(1):17-32
8158226
J Neurophysiol. 1994 Mar;71(3):1174-89
8201411
J Neurosci. 1996 Apr 1;16(7):2397-410
8601819
J Neurosci. 1997 Jan 1;17(1):204-15
8987749
J Neurophysiol. 1997 Apr;77(4):1697-715
9114230
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2665-70
9122253
J Neurophysiol. 1998 Jan;79(1):82-94
9425179
J Neurophysiol. 1998 May;79(5):2809-13
9582247
J Neurosci. 1998 Jun 15;18(12):4722-31
9614246
J Neurosci. 1998 Jul 1;18(13):5095-102
9634575
Dev Neurosci. 1998;20(2-3):125-45
9691188
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11450-5
9736757
J Neurophysiol. 1998 Sep;80(3):1558-61
9744960
Eur J Neurosci. 1998 Feb;10(2):664-72
9749727