title: Dopamine regulates two classes of primate prefrontal neurons that represent sensory signals.
abstract: The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing. Here, we tested the hypothesis that prefrontal DA regulates the representation of sensory signals that are required for perceptual decisions. In rhesus monkeys trained to report the presence or absence of visual stimuli at varying levels of contrast, we simultaneously recorded extracellular single-unit activity and applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes. In one population of neurons, DA suppressed activity with high temporal precision but preserved signal/noise ratio. Neurons in this group had short visual response latencies and comprised all recorded narrow-spiking, putative interneurons. In a distinct population, DA increased excitability and enhanced signal/noise ratio by reducing response variability. These neurons had longer visual response latencies and were composed exclusively of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and subsequently strengthening the representation of sensory signals, DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.
authors: Institute of Neurobiology, University of Tübingen, Tübingen, Germany. simon.jacob@charite.de
authors: Simon N
authors: SN
authors: Jacob
authors: Torben
authors: T
authors: Ott
authors: Andreas
authors: A
authors: Nieder
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D015350:Contrast Sensitivity / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D005133:Eye Movements; D007478:Iontophoresis; D008253:Macaca mulatta; D008297:Male; D009415:Nerve Net / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification* / Q000187:drug effects*; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000166:cytology*; D012372:ROC Curve; D011930:Reaction Time / Q000187:drug effects
chemical_list: D004298:Dopamine
references: Prog Neurobiol. 2004 Sep;74(1):1-58
references: 15381316
references: Nat Rev Neurosci. 2006 Dec;7(12):967-75
references: 17115078
references: J Neurosci. 1996 Mar 1;16(5):1922-35
references: 8774459
references: Science. 2001 Jan 12;291(5502):260-3
references: 11253215
references: J Neurophysiol. 2000 Mar;83(3):1733-50
references: 10712493
references: Science. 1979 Aug 31;205(4409):929-32
references: 112679
references: Annu Rev Neurosci. 1998;21:227-77
references: 9530497
references: Trends Cogn Sci. 2011 Dec;15(12):585-91
references: 22074811
references: Neuropsychopharmacology. 2006 Feb;31(2):297-309
references: 16012531
references: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19767-71
references: 22106310
references: J Neurosci. 1998 May 15;18(10):3870-96
references: 9570816
references: Nature. 2011 May 15;474(7351):372-5
references: 21572439
references: Neuron. 2000 Jun;26(3):695-702
references: 10896164
references: J Neurophysiol. 1998 Jul;80(1):1-27
references: 9658025
references: Science. 1990 Aug 24;249(4971):892-5
references: 2392679
references: J Neurophysiol. 2013 Jul;110(1):19-32
references: 23576697
references: Brain Res Rev. 2008 Aug;58(2):322-39
references: 18055018
references: Neuron. 1999 Aug;23(4):765-73
references: 10482242
references: J Neurophysiol. 1990 Jun;63(6):1385-400
references: 2358882
references: Nat Neurosci. 2002 Feb;5(2):175-80
references: 11802172
references: J Neurosci. 2013 Apr 24;33(17):7526-34
references: 23616557
references: Neuron. 2007 Jul 5;55(1):131-41
references: 17610822
references: J Neurophysiol. 2008 Jun;99(6):2985-97
references: 18400958
references: J Neurosci. 2003 Mar 1;23(5):1622-30
references: 12629166
references: Neuron. 2009 Dec 10;64(5):730-43
references: 20005828
references: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14266-71
references: 16924098
references: Neuron. 2012 Oct 4;76(1):1-11
references: 23040802
references: Nature. 2001 Aug 23;412(6849):787-92
references: 11518957
references: Nat Rev Neurosci. 2004 Oct;5(10):793-807
references: 15378039
references: Nat Rev Neurosci. 2009 Jan;10(1):48-58
references: 19050712
references: Nat Neurosci. 2010 Mar;13(3):369-78
references: 20173745
references: J Neurosci. 2011 Oct 5;31(40):14235-42
references: 21976508
references: Annu Rev Neurosci. 2007;30:259-88
references: 17600522
references: J Neurosci Methods. 1999 Jan;86(2):129-43
references: 10065982
references: Nature. 1995 Aug 17;376(6541):572-5
references: 7637804
references: Nat Rev Neurosci. 2008 Sep;9(9):696-709
references: 18714326
references: Biol Psychiatry. 2008 Nov 1;64(9):739-49
references: 18620336
references: Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):19900-9
references: 23086162
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2277-82
references: 20133872
references: Trends Neurosci. 2007 May;30(5):220-7
references: 17400299
references: Nature. 2008 Aug 28;454(7208):1110-4
references: 18633352
references: Cereb Cortex. 1998 Jun;8(4):321-45
references: 9651129
references: J Neurosci. 2008 Jul 30;28(31):7737-47
references: 18667606
references: Trends Neurosci. 2004 Nov;27(11):683-90
references: 15474169
references: J Neurosci Methods. 2006 Dec 15;158(2):207-11
references: 16843532
references: Nat Rev Neurosci. 2011 Nov 23;13(1):51-62
references: 22108672
references: Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6289-94
references: 22460793
references: Neuron. 2012 Oct 4;76(1):223-39
references: 23040817
references: Neuron. 2012 Jun 7;74(5):874-86
references: 22681691
references: Science. 2005 Mar 4;307(5714):1476-9
references: 15746431
references: J Comput Neurosci. 2001 Jul-Aug;11(1):63-85
references: 11524578
references: Nature. 2009 Jun 11;459(7248):837-41
references: 19448610
references: Trends Neurosci. 2007 May;30(5):194-202
references: 17408759
references: Nat Neurosci. 2005 Dec;8(12):1698-703
references: 16286929
references: Nat Rev Neurosci. 2010 Jul;11(7):474-89
references: 20531421
references: Neuron. 2003 May 8;38(3):433-45
references: 12741990
references: Nature. 2012 Aug 16;488(7411):343-8
references: 22878717
references: J Neurophysiol. 2000 Jul;84(1):390-400
references: 10899213
references: Nat Neurosci. 2003 Sep;6(9):968-73
references: 12897785
references: Neuroscience. 2012 Aug 30;218:181-4
references: 22626641
references: Neurosci Res. 2001 Oct;41(2):115-28
references: 11591439
references: Nat Neurosci. 2007 Mar;10(3):376-84
references: 17277774
references: Biol Psychiatry. 2011 Jun 15;69(12):e89-99
references: 21489408
references: Science. 2004 Feb 6;303(5659):853-6
references: 14764884
references: Exp Brain Res. 1969;9(3):221-35
references: 5371952