The Laboratory of Braulio Muñoz, PhD, is focused on studying the neurocircuitry of behaviors associated with motivation and habit learning, with special interest in the role and function of inhibitory transmission (GABA and glycine). The Muñoz Lab uses mouse models of addiction and neurodegenerative diseases (e.g. Parkinson's Disease), basic biochemical analyses (gene and protein expression assessments), electrophysiological measures on brain tissue, microscopy, and mouse behavioral assessments. The Muñoz Lab uses many different adeno-associated viral vector treatments to manipulate the function of brain cells and to measure their function in our physiological and behavioral measures to understand how the neurocircuitries are affected or regulate diseases states.
Active Research
The impact of alcohol on inhibitory corticostriatal transmission: Alcohol use disorders (AUDs) afflict millions of people in the United States and are a profound socioeconomic burden. AUDs and other addictive diseases include a shift from goal-directed to habitual, compulsive drug use. The striatum and its inputs from other brain regions such as the cortex, thalamus and amygdala play a critical role in the transition from goal-directed to habitual behaviors, including for drug use. It is important to understand how alcohol and other drugs of abuse alter striatum neural circuitry that governs this transition. Furthermore, it is important to explore the neural mechanisms whereby the striatum and its inputs determine goal-directed and habitual drug use. The project assesses the impact of alcohol on inhibitory neural transmission in these brain regions and how manipulations of neural circuitry alter alcohol drinking consumption behavior in addition to related behaviors such as reward perception, anxiety, locomotor responses, and motivation. It is hoped that by better understanding of the interactions between alcohol and the striatum inhibitory neurocircuits will reveal new and better therapeutics for treating AUDs.
Interactions between glycine receptor and alcohol drinking on dopaminergic function: Recent studies reported the presence of alpha 1 and 2-containing GlyRs in other brain regions, such as nucleus accumbens, dorsal striatum and cerebral cortex. GlyRs activation decreases neuronal excitability associated with sensorial information, motor control, and respiratory functions; all of which are significantly altered during alcohol intoxication. We previously demonstrated that GlyR beta subunit plays a role in the modulation by alcohol and other positive allosteric modulators in alpha 2-containing GlyRs. Interestingly, D1 MSNs (dMSNs) in the nucleus accumbens express GlyRs that are highly sensitive to alcohol and dopamine modulation, while D2 MSNs (iMSNs) are potentiated but in a minor manner. In this project we are investigating how dorsal striatal tonic glycinergic currents that are modulated by binge alcohol consumption. In addition, we are seeking to determine how alcohol consumption interacts with dopamine release and or lesion affecting the role of tonic glycinergic currents regulating the excitatory-inhibitory balance within the dorsal striatum.
The impact of dopamine lesion on glycine receptor mediating AUD and Parkinson’s disease progression: As AUDs, Parkinson’s disease (PD) affects millions of people worldwide. Interestingly, AUDs and PD affects the basal ganglia, playing a key role in regulating striatal reward and motor circuits. Currently, there is no treatment to delay or stop the progression of PD. There has been little work done to determine the lasting impact of glycine receptors on the progression of AUDs and PD of alcohol- and motor related behaviors later in life and on physiology. Making glycine receptors an interesting pharmacological target to treat AUDs and PD. This project goal is to determine the role of glycine receptors on mitigating PD progression.
PLUS Award
Role of striatal Glycine Receptors in alcohol binge consumption.
07/01/2023-06/30/2025
Role: Principal Investigator (20% effort)
CTSI Project Development Award
Role of corticostriatal GABA transmission in alcohol consumption
06/13/2022-06/01/2025
Role: Principal Investigator (20% effort)
NIH/NIAAA R01 AA030955
Impact of prenatal opioid exposure on corticostriatal circuits that modulate alcohol-related
behaviors
09/20/2018-08/31/2023
Role: Co-Investigator (60% effort) (PI: Atwood)
Recent Publications
Muñoz B and Atwood BK. (2024). Alcohol consumption does not impact delta and kappa opioid receptor-mediated synaptic depression in dorsolateral striatum of adult male mice. Alcohol. 10.1016/j.alcohol.2024.06.002. PMID: 38857678.
Muñoz B and Atwood BK. (2023). A novel inhibitory corticostriatal circuit that expresses mu opioid receptor-mediated synaptic plasticity. Neuropharmacology. 10.1016/j.neuropharm.2023.109696. PMID: 37659438.
Sanhueza S, Vidal MA, Hernandez MA, Henriquez-Beltran ME, Cabrera C, Quiroga R, Antilef BE, Aguilar KP, Castillo DA, Llerena FJ, Fraga Figueroa M, Nazal M, Castro E, Lagos P, Moreno A, Lastra JJ, Gajardo J, Garcés P, Riffo B, Buchert J, Sanhueza R, Ormazábal V, Saldivia P, Vargas C, Nourdin G, Koch E, Zuñiga FA, Lamperti L, Bustos P, Guzmán-Gutiérrez E, Aguayo Tapia C, Ferrada L, Cerda G, Woehlbier U, Riquelme E, Yuseff MI, Muñoz B, Lombardi G, De Gonzalo-Calvo D, Salomon C, Verdugo RA, Quiñones LA, Colombo A, Barría MI, Labarca G and Nova-Lamperti E. (2023). Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome. Frontiers in Medicine Infectious Diseases: Pathogenesis and Therapy. 0.3389/fmed.2023.1271863. PMID: 37869162.
Haggerty DL, Muñoz B, Pennington T, Viana Di Prisco G, Grecco GG and Atwood BK. (2022). The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking. eLife. 11:e77411. PMID: 36098397.
Muñoz B, Fritz BM, Yin F, and Atwood BK. (2022). HCN1 channels mediate mu opioid receptor long-term depression at insular cortex inputs to the dorsal striatum. Journal of Physiology. 10.1113/JP283513. PMID: 36181477.
Reeves K, Shah N, Muñoz B, and Atwood BK. (2022). Opioid receptor-mediated regulation of neurotransmission in the brain. Frontiers in Molecular Neuroscience. 10.3389/fnmol.2022.919773. PMID: 35782382.
Grecco GG, Muñoz B, Viana Di Prisco G, Doud EH, Fritz BM, Maulucci D, Gao Y, Mosley, AL, Baucum AJ, and Atwood BK. (2022). Prenatal opioid exposure impairs endocannabinoid and glutamate transmission in the dorsal striatum. eNeuro. 10.1523/ENEURO.0119-22.2022. PMID: 35396255.
Grecco GG, Huang JY, Muñoz B, Doud EH, Hines CD, Gao Y, Rodriguez B, Mosley AL, Lu HC, and Atwood BK. (2022). Sex-Dependent synaptic remodeling of the somatosensory cortex in mice with prenatal methadone exposure. Advances in Drug and Alcohol Research. 10.3389/adar.2022.10400.
Muñoz B, Mariqueo T, Murath P, Peters C, Yevenes GE, Moraga-Cid G, Peoples RW and Aguayo LG. (2021). Modulatory actions of the glycine receptor beta subunit on the positive allosteric modulation of ethanol in alpha 2 containing receptors. Frontiers in Molecular Neuroscience. doi.org/10.3389/fnmol.2021.763868. PMID: 34867189.
Araya A, Gallegos S, Viveros R, San Martin L, Muñoz B, Harvey RJ, Zeilhofer HU and Aguayo LG. (2021). Presence of ethanol sensitive and insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice. British Journal of Pharmacology. doi: 10.1111/bph.15649. PMID: 34378188.
Fernandez-Perez EJ, Muñoz B, Bacuñan DA, Peters C, Riffo-Lepe NO, Espinoza MP, Morgan PJ, Filippi C, Bourboulou R, Sengupta U, Kayed R, Epsztein J and Aguayo LG. (2020). Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers. Aging Cell. 10.1111/acel.13455. PMID: 34409748.
Cisternas P, Taylor X, Perkins A, Maldonado O, Allman E, Cordova R, Marambio Y, Muñoz B, Pennington T, Xiang S, Zhang J, Vidal R, Atwood BK and Lasagna-Reeves CA. (2020). Vascular amyloid accumulation alters the GABAergic synapse and induces hyperactivity in a model of cerebral amyloid angiopathy. Aging Cell. Oct;19(10):e13233. PMID: 32914559.
Reeves KC, Kube MJ, Grecco GG, Fritz BM, Muñoz B, Yin F, Gao Y, Haggerty DL, Hoffman HJ and Atwood BK. (2020). Mu opioid receptors on vGluT2‐expressing glutamatergic neurons modulate opioid reward. Addiction Biology. e12942. PMID: 32686251
Muñoz B, Gallegos S, Peters C, Murath P, Lovinger DM, Homanics GE and Aguayo LG. (2020). Influence of nonsynaptic α1 glycine receptors on ethanol consumption and place preference. Addiction Biology. 25(2):e12726. PMID: 30884072.
Muñoz B, Haggerty D and Atwood BK. (2020). Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum. Scientific Reports. 10 (1):7234. PMID: 32350330.
Moraga-Cid G, San Martin VP, Lara CO, Muñoz B, Marileo AM, Sazo A, Muñoz-Montesino C, Fuentealba J, Castro PA, Guzman L, Burgos CF, Zeilhofer HU, Aguayo LG, Corringer PJ and Yevenes GE. (2020). Modulation of glycine receptor single-channel conductance by intracellular phosphorylation. Scientific Reports. 10 (1):4804. PMID: 32179786.
Fritz BM, Muñoz B and Atwood BK. (2019). Genetic selection for alcohol preference in mice alters dorsal striatum neurotransmission. Alcoholism Clinical and Experimental Research. 43(11):2312-2321. PMID: 31491046.
Gallegos S, Muñoz B, Araya A, and Aguayo LG. (2019). High ethanol sensitive glycine receptors regulate firing in D1 medium spiny neurons in the nucleus accumbens. Neuropharmacology. 160:107773. PMID: 31521620.
Jay TR, von Saucken VE, Muñoz B, Codocedo JF, Atwood BK, Lamb BT and Landreth GE. (2019). TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment. Glia. 67(10):1873-1892. PMID: 31265185.
You Y, Perkins A, Cisternas P, Muñoz B, Taylor X, You Y, Barringer HJ, Oblak AL, Atwood BK, Vidal R and Lasagna-Reeves CA. (2019). Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy. Acta Neuropathologica Communications. 7(1):26. PMID: 30808415.
Muñoz B, Yevenes GE, Forstera B, Lovinger DM. Homanics GE, Harvey RJ and Aguayo LG. (2018). Presence of inhibitory glycinergic transmission in medium spiny neurons in the nucleus accumbens. Frontiers in Molecular Neuroscience. 11:228. PMID: 30050406.
Muñoz B, Fritz BM, Yin F and Atwood BK. (2018). Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum. Nature Communications. 9(1): 1318. PMID: 29615610.
Forstera B, Muñoz B, Lobo MK, Chandra R, Lovinger DM and Aguayo LG. (2017). Presence of ethanol sensitive glycine receptors in medium spiny neurons in the nucleus accumbens. Journal of Physiology. 595 (15) 5285-5300. PMID: 28524260.
Fritz BM, Muñoz B, Yin F, Bauchle C and Atwood BK. (2017) A high fat, high-sugar ‘Western’ diet alters dorsal striatal glutamate, opioid, and dopamine transmission in mice. Neuroscience. 372 1-15. PMID: 29289718.
Acuña MA, Yevenes GE, Ralvenius WT, Di Lio A, Lara CO, Muñoz B, Burgos CF, Moraga-Cid G, Corringer PJ and Zeilhofer HU. (2016). Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain. The Journal of Clinical Investigation. 126(7):2547-60. PMID: 27270175.
Lara CO, Murath P, Muñoz B, Marileo, AM, San Martín L, San Martín VP, Burgos CF, Mariqueo TA, Aguayo LG, Fuentealba J, Godoy P, Guzmán J and Yevenes GE. (2016). Functional modulation of glycine receptors by the alkaloid gelsemine. British Journal of Pharmacology. 173, 14:2263-2277. PMID: 27128379.
Burgos CF, Muñoz B, Guzman JL, Aguayo LG. (2015). Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses. Pharmacological Research. 101:18-29. PMID: 26158502.
Aguayo LG, Castro P, Mariqueo T, Munoz B, Xiong W, Zhang L, Lovinger DM, Homanics GE. (2014). Altered sedative effects of ethanol in mice with α1 glycine receptor subunits that are insensitive to Gβγ modulation. Neuropsychopharmacology. 39, 2538-2548. PMID: 24801766.
Mariqueo T, Agurto A, Muñoz B, San Martin L, Coronado C, Fernandez-Perez F, Sanchez A, Homanics GE and Aguayo LG (2014). Effects of ethanol on glycinergic synaptic currents in mouse spinal cord neurons. Journal of Neurophysiology. 111,10: 1940-1948. PMID: 24572089.
San Martin L, Cerda F, Jimenez V, Fuentealba J, Muñoz B, Aguayo LG and Guzman L. (2012). Inhibition of the ethanol-induced potentiation of α1 glycine receptor by a small peptide that interferes with Gβγ binding. The Journal of Biological Chemistry. 287: 40713-40721. PMID: 23035114.
Peters C, Muñoz B, Sepúlveda FJ, Urrutia J, Quiroz M, Luza S, De Ferrari GV, Aguayo LG, Opazo C. (2011). Biphasic effects of copper on neurotransmission in rat hippocampal neurons. Journal of Neurochemistry. 119:78-88. PMID: 21824141
Fuentealba J, Muñoz B, Yevenes G, Guzmán L, Moraga-Cid G, Pérez C, Manriquez-Navarro P, Becerra J, Silva M and Aguayo LG. (2010). Potentiation and inhibition of glycine receptors by tutin. Neuropharmacology. 2-3:453-459. PMID: 21824141
