Abstract
Early-onset drinking during childhood or preadolescence is a serious social problem. Yet, most of the basic neurobiological research on the acute effects of ethanol has been carried out on adult or early postnatal animals. We studied the effect of alcohol exposure on the basic electrophysiological properties and cell viability of layer 5 pyramidal neurons from the somatosensory cortex of juvenile (P21–P23) C57BL/6N mice. After bath application of 50 mM ethanol to acute slices of the somatosensory cortex, no adverse effects were detected on cells survival, whereas the input resistance and firing rate of layer 5 neurons were significantly reduced. While the effect on the input resistance was reversible, the depressing effect on cell firing remained stable after 6 min of alcohol exposure. Ethanol application did not result in any significant change of mIPSC frequency, amplitude, and rise time. A slight increase of mIPSC decay time was observed after 6 min of ethanol exposure. The molecular mechanisms leading to these alterations and their significance for the physiology of the cerebral cortex are briefly discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Atkinson SE, Williams SR (2009) Postnatal development of dendritic synaptic integration in rat neocortical pyramidal neurons. J Neurophysiol 102:735–751. https://doi.org/10.1152/jn.00083.2009
Badanich KA, Mulholland PJ, Beckley JT, Trantham-Davidson H, Woodward JJ (2013) Ethanol reduces neuronal excitability of lateral orbitofrontal cortex neurons via a glycine receptor dependent mechanism. Neuropsychopharmacology 38:1176–1188. https://doi.org/10.1038/npp.2013.12
Brodie MS, Appel SB (2000) Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation. Alcohol Clin Exp Res 24:1120–1124
Chen Y, Wu P, Fan X, Chen H, Yang J, Song T, Huang C (2012) Ethanol enhances human hyperpolarization-activated cyclic nucleotide-gated currents. Alcohol Clin Exp Res 36:2036–2046. https://doi.org/10.1111/j.1530-0277.2012.01826.x
Cohen EJ, Quarta E, Bravi R, Granato A, Minciacchi D (2017) Neural plasticity and network remodeling: from concepts to pathology. Neuroscience 344:326–345. https://doi.org/10.1016/j.neuroscience.2016.12.048
Criswell HE, Ming Z, Kelm MK, Breese GR (2008) Brain regional differences in the effect of ethanol on GABA release from presynaptic terminals. J Pharmacol Exp Ther 326:596–603. https://doi.org/10.1124/jpet.107.135418
Day M, Carr DB, Ulrich S, Ilijic E, Tkatch T, Surmeier DJ (2005) Dendritic excitability of mouse frontal cortex pyramidal neurons is shaped by the interaction among HCN, Kir2, and Kleak channels. J Neurosci 25:8776–8787
Donovan JE (2009) Estimated blood alcohol concentrations for child and adolescent drinking and their implications for screening instruments. Pediatrics 123:e975–e981. https://doi.org/10.1542/peds.2008-0027
Donovan JE (2013) The burden of alcohol use: focus on children and preadolescents. Alcohol Res 35:186–192
Dou X, Wilkemeyer MF, Menkari CE, Parnell SE, Sulik KK, Charness ME (2013) Mitogen-activated protein kinase modulates ethanol inhibition of cell adhesion mediated by the L1 neural cell adhesion molecule. Proc Natl Acad Sci USA 110:5683–5688. https://doi.org/10.1073/pnas.1221386110
Ehrlich D, Pirchl M, Humpel C (2012) Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices. Brain Res 1459:35–42. https://doi.org/10.1016/j.brainres.2012.04.020
Fleming RL, Manis PB, Morrow AL (2009) The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons. Alcohol 43:603–618. https://doi.org/10.1016/j.alcohol.2009.10.006
Förstera B, Castro PA, Moraga-Cid G, Aguayo LG (2016) Potentiation of gamma aminobutyric acid receptors (GABAAR) by ethanol: how are inhibitory receptors affected? Front Cell Neurosci 10:114. https://doi.org/10.3389/fncel.2016.00114
Fuenzalida M, Fernandez de Sevilla D, Buño W (2007) Changes of the EPSP waveform regulate the temporal window for spike-timing-dependent plasticity. J Neurosci 27:11940–11948
Galindo R, Zamudio PA, Valenzuela CF (2005) Alcohol is a potent stimulant of immature neuronal networks: implications for fetal alcohol spectrum disorder. J Neurochem 94:1500–1511
Gilpin NW, Smith AD, Cole M, Weiss F, Koob GF, Richardson HN (2009) Operant behavior and alcohol levels in blood and brain of alcohol-dependent rats. Alcohol Clin Exp Res 33:2113–2123. https://doi.org/10.1111/j.1530-0277.2009.01051.x
Granato A, Palmer LM, De Giorgio A, Tavian D, Larkum ME (2012) Early exposure to alcohol leads to permanent impairment of dendritic excitability in neocortical pyramidal neurons. J Neurosci 32:1377–1382. https://doi.org/10.1523/JNEUROSCI.5520-11.2012
Han CL, Liao CS, Wu CW, Hwong CL, Lee AR, Yin SJ (1998) Contribution to first-pass metabolism of ethanol and inhibition by ethanol for retinol oxidation in human alcohol dehydrogenase family–implications for etiology of fetal alcohol syndrome and alcohol-related diseases. Eur J Biochem 254:25–31
Heit C, Dong H, Chen Y, Shah YM, Thompson DC, Vasiliou V (2015) Transgenic mouse models for alcohol metabolism, toxicity, and cancer. Adv Exp Med Biol 815:375–387. https://doi.org/10.1007/978-3-319-09614-8_22
Hingson RW, Heeren T, Winter MR (2006) Age at drinking onset and alcohol dependence: age at onset, duration, and severity. Arch Pediatr Adolesc Med 160:739–746
Huang JJ, Yen CT, Tsai ML, Valenzuela CF, Huang C (2012) Acute ethanol exposure increases firing and induces oscillations in cerebellar Golgi cells of freely moving rats. Alcohol Clin Exp Res 36:2110–2116. https://doi.org/10.1111/j.1530-0277.2012.01818.x
Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Hörster F, Tenkova T, Dikranian K, Olney JW (2000) Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287:1056–1060
Lobo IA, Harris RA (2008) GABA(A) receptors and alcohol. Pharmacol Biochem Behav 90:90–94. https://doi.org/10.1016/j.pbb.2008.03.006
Lotfullina N, Khazipov R (2017) Ethanol and the developing brain: inhibition of neuronal activity and neuroapoptosis. Neuroscientist. https://doi.org/10.1177/1073858417712667
Marszalec W, Aistrup GL, Narahashi T (1998) Ethanol modulation of excitatory and inhibitory synaptic interactions in cultured cortical neurons. Alcohol Clin Exp Res 22:1516–1524
McMurray MS, Amodeo LR, Roitman JD (2016) Consequences of adolescent ethanol consumption on risk preference and orbitofrontal cortex encoding of reward. Neuropsychopharmacology 41:1366–1375. https://doi.org/10.1038/npp.2015.288
Moriguchi S, Zhao X, Marszalec W, Yeh JZ, Narahashi T (2007) Effects of ethanol on excitatory and inhibitory synaptic transmission in rat cortical neurons. Alcohol Clin Exp Res 31:89–99
Okamoto T, Harnett MT, Morikawa H (2006) Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J Neurophysiol 95:619–626
Olney JW (2014) Focus on apoptosis to decipher how alcohol and many other drugs disrupt brain development. Front Pediatr 2:81. https://doi.org/10.3389/fped.2014.00081
Proctor WR, Soldo BL, Allan AM, Dunwiddie TV (1992) Ethanol enhances synaptically evoked GABAA receptor-mediated responses in cerebral cortical neurons in rat brain slices. Brain Res 595:220–227
Ramaswamy S, Markram H (2015) Anatomy and physiology of the thick-tufted layer 5 pyramidal neuron. Front Cell Neurosci 9:233. https://doi.org/10.3389/fncel.2015.00233
Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J (2009) Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373:2223–2233. https://doi.org/10.1016/S0140-6736(09)60746-7
Sanderson JL, Donald Partridge L, Valenzuela CF (2009) Modulation of GABAergic and glutamatergic transmission by ethanol in the developing neocortex: an in vitro test of the excessive inhibition hypothesis of fetal alcohol spectrum disorder. Neuropharmacology 56:541–555. https://doi.org/10.1016/j.neuropharm.2008.10.012
Sessler FM, Hsu FC, Felder TN, Zhai J, Lin RC, Wieland SJ, Kosobud AE (1998) Effects of ethanol on rat somatosensory cortical neurons. Brain Res 804:266–274
Siggins GR, Pittman QJ, French ED (1987) Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414:22–34
Smolen TN, Smolen A (1989) Blood and brain ethanol concentrations during absorption and distribution in long-sleep and short-sleep mice. Alcohol 6:33–38
Spear LP (2016) Consequences of adolescent use of alcohol and other drugs: studies using rodent models. Neurosci Biobehav Rev 70:228–243. https://doi.org/10.1016/j.neubiorev.2016.07.026
Tipps ME, Raybuck JD, Lattal KM (2014) Substance abuse, memory, and post-traumatic stress disorder. Neurobiol Learn Mem 112:87–100. https://doi.org/10.1016/j.nlm.2013.12.002
Trudell JR, Messing RO, Mayfield J, Harris RA (2014) Alcohol dependence: molecular and behavioral evidence. Trends Pharmacol Sci 35:317–323. https://doi.org/10.1016/j.tips.2014.04.009
Wei W, Faria LC, Mody I (2004) Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABAA receptors in hippocampal neurons. J Neurosci 24:8379–8382
Weiner JL, Valenzuela CF (2006) Ethanol modulation of GABAergic transmission: the view from the slice. Pharmacol Ther 111:533–554
White AM (2003) What happened? Alcohol, memory blackouts, and the brain. Alcohol Res Health 27:186–196
Yan H, Li Q, Fleming R, Madison RD, Wilson WA, Swartzwelder HS (2009) Developmental sensitivity of hippocampal interneurons to ethanol: involvement of the hyperpolarization-activated current, Ih. J Neurophysiol 101:67–83. https://doi.org/10.1152/jn.90557.2008
Zorumski CF, Mennerick S, Izumi Y (2014) Acute and chronic effects of ethanol on learning-related synaptic plasticity. Alcohol 48:1–17. https://doi.org/10.1016/j.alcohol.2013.09.045
Author information
Authors and Affiliations
Contributions
FF designed and performed the experiments, analyzed the data, and wrote the manuscript. BD designed and performed the experiments and analyzed the data. ADG performed the experiments and analyzed the data. LL performed the experiments and analyzed the data. AG designed and performed the experiments, analyzed the data, and wrote the manuscript. All the authors have read and approved the manuscript.
Corresponding author
Rights and permissions
About this article
Cite this article
Ferrini, F., Dering, B., De Giorgio, A. et al. Effects of Acute Alcohol Exposure on Layer 5 Pyramidal Neurons of Juvenile Mice. Cell Mol Neurobiol 38, 955–963 (2018). https://doi.org/10.1007/s10571-017-0571-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-017-0571-4