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  Noradrenergic Modulation of Spontaneous Activity and Sensoryevoked Responses in Prefrontal Cortex

Eschenko, O., Pietrajtis, K., Sara, S., & Logothetis, N. (2010). Noradrenergic Modulation of Spontaneous Activity and Sensoryevoked Responses in Prefrontal Cortex. Poster presented at AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles, Santorini, Greece.

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http://www.areadne.org/2010/home.html (Publisher version)
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 Creators:
Eschenko, O1, 2, Author              
Pietrajtis, K1, 2, Author              
Sara, SJ, Author
Logothetis, NK1, 2, Author              
Affiliations:
1Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497798              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Neural coding in medial prefrontal cortex (mPFC) is thought to underlie various cognitive behaviors such as rule-guided learning, strategy use, or cognitive flexibility. Specifically, prefrontal neurons display many behaviorally relevant correlates related to sensory perception, motor responses, or reward that are believed to contribute to behavioral outcome. The mPFC is the cortical region that receives exceptionally dense dopaminergic (DA) innervation arising from the mesopontine Ventral Tegmental Area (VTA). Noradrenergic fibers originating from the brain stem nucleus Locus Coeruleus (LC) are also dense in mPFC. Previous investigations indicated that NA and DA systems have common target neurons in mPFC. The ascending NA and DA projections to mPFC have been implicated in a broad range of cognitive processes in rodents and primates including modulation of perception, attention, motivation, or memory. It is still, however, unknown whether and how NA and DA affect the prefrontal neural codes. To address this question, we performed simultaneous recordings of unit activity and local field potentials in mPFC, VTA and LC in the rat. We first studied temporal relations of firing activity in the three brain regions during spontaneous and evoked activity under anesthesia. Mild electric shocks were applied to the rat hind paw for somatosensory stimulation. The LC neurons responded to a single foot shock (1ms, 5mA) with a short latency (~20ms), phasic burst, followed by brief inhibition. Trains of pulses (100ms, 50Hz, 5mA) elicited much stronger responses. The mPFC and VTA neurons did not respond to a single foot shock. Trains elicited sustained (~1s) excitatory responses in a subpopulation of mPFC neurons with latencies of ~100ms, usually followed by inhibition. Trains elicited both excitatory and inhibitory responses in a small number of putative dopaminergic, VTA cells, with latencies always greater than 100ms. Both spontaneous and evoked activity of VTA neurons was highly synchronized with mPFC activity; cortical activity always led VTA by several milliseconds. In some cases, sensory stimulation resulted in entrainment of mPFC and VTA neurons in several cycles of slow oscillation. Next, we inhibited the LC by systemic or local application of clonidine, an α2-adrenergic receptor agonist. This manipulation dramatically abolished the excitatory evoked responses in both VTA and mPFC without having much effect on spontaneous activity. The results indicate that short-latency responses of LC neurons to somatosensory stimulation with corresponding release of NA modulate sensory responses in the target regions including mPFC and VTA. The long-latency responses of the VTA cells suggest that its ascending projections do not play an important role in modulating mPFC responses to noxious stimuli. VTA activity is rather driven by mPFC and, possibly, modulated by LC. We will further investigate NA modulation of mPFC codes in the rat performing a prefrontaldependent task. To induce release of NA in mPFC, we will apply electrical microstimulation to the LC just before presentation of discrimination stimuli, mimicking the burst activity of LC typically observed in response to salient stimuli. We expect to see more robust coding in the mPFC correlated with better behavioral performance in the presence of LC activation.

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 Dates: 2010-06
 Publication Status: Published in print
 Pages: -
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 Rev. Type: -
 Identifiers: BibTex Citekey: 6814
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Title: AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles
Place of Event: Santorini, Greece
Start-/End Date: 2010-06-17 - 2010-06-20

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Title: AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles
Source Genre: Proceedings
 Creator(s):
Hatsopoulos, NG, Editor
Pezaris, JS, Editor
Affiliations:
-
Publ. Info: -
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: 60 Identifier: ISSN: 2155-3203