Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex.
The specific functions of subtypes of cortical inhibitory neurons are not well understood. This is due in part to a dearth of information about the behaviors of interneurons under conditions when the surrounding circuit is in an active state. We investigated the firing behavior of a subset of inhibitory interneurons, identified using mice that express green fluorescent protein (GFP) in a subset of somatostatin-expressing inhibitory cells ("GFP-expressing inhibitory neuron" [GIN] cells). The somata of the GIN cells were in layer 2/3 of somatosensory cortex and had dense, layer 1-projecting axons that are characteristic of Martinotti neurons. Interestingly, GIN cells fired similarly during a variety of diverse activating conditions: when bathed in fluids with low-divalent cation concentrations, when stimulated with brief trains of local synaptic inputs, when exposed to group I metabotropic glutamate receptor agonists, or when exposed to muscarinic cholinergic receptor agonists. During these manipulations, GIN cells fired rhythmically and persistently in the theta-frequency range (3-10 Hz). Synchronous firing was often observed and its strength was directly proportional to the magnitude of electrical coupling between GIN cells. These effects were cell type specific: the four manipulations that persistently activated GIN cells rarely caused spiking of regular-spiking (RS) pyramidal cells or fast-spiking (FS) inhibitory interneurons. Our results suggest that supragranular GIN interneurons form an electrically coupled network that exerts a coherent 3- to 10-Hz inhibitory influence on its targets. Because GIN cells are more readily activated than RS and FS cells, it is possible that they act as "first responders" when cortical excitatory activity increases.
Fanselow
Erika E
EE
Department of Neurobiology, University of Pittsburgh School of Medicine, W1458 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop St., Pittsburgh, PA 15261, USA. circuit@pitt.edu
Richardson
Kristen A
KA
Connors
Barry W
BW
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009116:Muscarine / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D049452:Green Fluorescent Proteins; D009116:Muscarine; D010852:Picrotoxin; D011724:Pyridazines; D013004:Somatostatin; C049853:gabazine
Neuron. 2001 Aug 16;31(3):477-85
11516403
Curr Opin Neurobiol. 2006 Dec;16(6):710-5
17011181
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6144-9
10823957
J Neurophysiol. 1997 May;77(5):2427-45
9163368
J Neurophysiol. 1989 Feb;61(2):311-30
2918357
Nat Neurosci. 1998 Aug;1(4):279-85
10195160
Nat Neurosci. 2000 Oct;3(10):1027-34
11017176
J Chem Neuroanat. 2003 Dec;26(4):233-42
14729126
J Neurophysiol. 1996 Feb;75(2):951-7
8714667
J Neurophysiol. 2003 Nov;90(5):2987-3000
12815025
Nature. 1995 Feb 16;373(6515):612-5
7854418
Neuroscience. 1991;41(2-3):365-79
1870696
J Neurosci. 2005 Aug 10;25(32):7309-16
16093380
J Neurosci. 2000 May 1;20(9):3354-68
10777798
Cereb Cortex. 2003 May;13(5):500-7
12679296
Nat Neurosci. 2007 Jun;10(6):743-53
17515899
Neuroscience. 2000;95(4):933-52
10682701
Nat Neurosci. 2000 Sep;3(9):904-10
10966621
Nat Neurosci. 2007 Apr;10(4):462-8
17334362
J Clin Neurophysiol. 1992 Apr;9(2):212-23
1350591
Curr Opin Neurobiol. 2001 Dec;11(6):739-44
11741027
Neuron. 2002 Jan 31;33(3):325-40
11832222
J Physiol. 1986 Jun;375:169-94
2879035
Nature. 2004 Oct 14;431(7010):796-803
15483601
J Neurosci. 2005 Jan 26;25(4):1024-33
15673684
Neurobiol Learn Mem. 2003 Nov;80(3):245-56
14521867
J Neurosci. 2007 Feb 21;27(8):2058-73
17314301
J Neurosci. 1999 Sep 1;19(17):7603-16
10460266
J Neurophysiol. 2000 May;83(5):2802-13
10805678
Science. 1991 Jan 25;251(4992):432-5
1824881
Nature. 1995 Nov 2;378(6552):75-8
7477292
Nature. 2003 May 15;423(6937):288-93
12748642
J Neurophysiol. 1978 May;41(3):798-820
660231
J Neurosci. 1996 Apr 15;16(8):2701-15
8786446
Neuron. 2003 Jun 5;38(5):805-17
12797964
Nature. 1999 Nov 4;402(6757):75-9
10573419
Eur J Neurosci. 2001 Feb;13(4):657-69
11207801
J Comp Neurol. 2006 Nov 1;499(1):144-60
16958092
J Neurosci. 2006 May 10;26(19):5069-82
16687498
J Neurophysiol. 2006 Aug;96(2):834-45
16707715
J Neurophysiol. 2006 Mar;95(3):1630-8
16207788
J Physiol. 1957 Jul 11;137(2):218-44
13449874
J Neurophysiol. 2003 Jul;90(1):333-41
12612003
Neuron. 2007 Mar 1;53(5):735-46
17329212
J Comp Neurol. 2003 May 12;459(4):407-25
12687707
Science. 2006 Sep 15;313(5793):1626-8
16973878
J Neurosci. 2002 May 15;22(10):4142-52
12019332
J Physiol. 2004 Nov 15;561(Pt 1):65-90
15331670
J Neurophysiol. 1998 Feb;79(2):567-82
9463422
J Neurophysiol. 1989 Apr;61(4):747-58
2542471