Miller, Mark W., PhD

Professor
Dr. Mark W. Miller

Contact Info

  • Medical Sciences Campus
    Dr. Guillermo Arbona Irizarry Bldg.
    5th Floor, Office A563C

    Institute of Neurobiology
    Lab 112

  • 787-721-4149 x269

Research Interests

Rhythmic activities in the nervous system of invertebrates.

Our research focuses on the neuronal circuits that govern behavior. We use several marine invertebrate animal models, due to the advantageous properties of their simple nervous systems. In the blue crab, Callinectes sapidus, we are investigating how the central system regulates the heartbeat, and specifically how neuromodulators achieve such modulation via coordinated central and peripheral actions. In the marine mollusk, Aplysia californica, we have identified key interneurons that regulate feeding behavior using two classical neurotransmitters, GABA and dopamine. These studies increase our understanding of the neural control of behavior in all animals, including humans. They should also provide insight into fundamental neuronal mechanism that underlines maladaptive brain activities. Techniques included in the laboratory include intracellular and extracellular recording, dye injection of neurons, nerve backfills, immunohistochemistry and confocal microscopy.

A new project in the lab uses a parasite-host as a model system for studying neuronal circuits governing behavior. The digenetic trematode Schistosoma mansoni that causes the form of schistosomiasis found in the Western Hemisphere requires the freshwater snail Biomphalaria glabrata as its primary intermediate host. It has been proposed that the transition from the free-living S. mansoni miracidium to parasitic mother sporocyst depends upon uptake of biogenic amines, e.g. serotonin, from the snail host. However, little is known about potential sources of serotonin in B. glabrata tissues. This investigation examines the localization of serotonin-like immunoreactivity (5HTli) in the central nervous system (CNS) and peripheral tissues of B. glabrata. Emphasis is placed upon the cephalic and anterior pedal regions that are commonly the sites of S. mansoni miracidium penetration. The anterior foot and body wall are densely innervated by 5HTli fibers but no peripheral immunoreactive neuronal somata have been detected. Within the CNS, clusters of 5HTli neurons are observed in the cerebral, pedal, left parietal, and visceral ganglia, suggesting that the peripheral serotonergic fibers originate from the CNS. Double-labeling experiments (biocytin backfill x serotonin immunoreactivity) of the tentacular nerve and the three major pedal nerves (Pd n. 10, Pd n. 11, and Pd n. 12) have disclosed central neurons that project to the cephalopedal periphery. Overall, the central distribution of 5HTli neurons suggests that, as in other gastropods, serotonin regulates the locomotion, reproductive, and feeding systems of Biomphalaria. The projections to the foot and body wall indicate that serotonin may also participate in defensive, nociceptive, or inflammation responses. These observations identify potential sources of host-derived serotonin in this parasite-host.

Another project in the lab is titled “Estuary systems: Consequences of estuary contamination on crab heart and neurosecretory systems”. These studies focus on a ubiquitous crustacean inhabitant of the San Juan Bay Estuary, the blue crab Callinectes sapidus, as an experimental model for assessing effects of anthropogenic factors on nervous system function.  This species is native to waters of the western Atlantic, ranging from northern Argentina to as far north as Nova Scotia and supports one of the largest fisheries industries in the United States, estimated at more than 100 million dollars in 2005.  However, alarming decreases in its populations have been documented in recent years. The central hypothesis of this project posits that pollutants can exert significant sub-lethal effects on nervous system structure and function. This project is comprised of three objectives that will explore this hypothesis: 1) develop bioprobes to monitor levels of contaminants in sediments, water and crab tissue samples in the SJBE; 2) assess the impact of contaminants and oxygen levels on the cardiac system of crabs obtained from distinct environmental condition; and finally, 3) assess the impact of contaminants and oxygen levels on the sinus gland neurosecretory system of crabs obtained from distinct environmental conditions.

Present Funding:

NIH COBRE, NSF CREST, NSF PIRE, NSF OSIB, NSF ORCC-SCORES

Selected Publications:

  • Rolón-Martinez S, Habid MR, Mansour TA, Diaz-Rios M, Rosenthal JJC, Zhou XN, Croll RP, Miller MW (2021) FMRF-NH2-related neuropeptides in Biomphalaria spp., intermediate hosts for schistosomiasis: Precursor organization and immunohistochemical localization. J Comp Neurol. 2021 Sep;529(13):3336-3358. doi: 10.1002/cne.25195. Epub 2021 Jun 11. PMID: 34041754
  • Rosa-Casillas M, de Jesús PM, Vicente-Rodriguez LC, Habib MR, Croll RP, Miller MW (2021) Identification and localization of a gonadotropin-releasing hormone-related neuropeptide in Biomphalaria, an intermediate host for schistosomiasis. J Comp Neurol, Jun; 529(9):2347-2361. doi: 10.1002/cne.25099. Epub 2021 Jan 27. PMID: 33368267
  • Habib MR, Ghoname SI, Ali RE, El-Karim RMG, Youssef AA, Croll RP, Miller MW (2020) Biochemical and apoptotic changes in the nervous and ovotestis tissues of Biomphalaria alexandrina following infection with Schistosoma mansoni. Exp Parasitol Mar 26; 213:107887 doi: 10.1016/j.exppara.2020.107887. PMID: 32224062
  • Acker MJ, Habib MR, Beach GA, Doyle JM, Miller MW, Croll RP (2019) An immunohistochemical analysis of peptidergic neurons apparently associated with reproduction and growth in Biomphalaria alexandrina. Gen Comp Endocrinol. 2019 Sep 1;280:1-8. doi: 10.1016/j.ygcen.2019.03.017. Epub 2019 Mar 26. PMID: 30923005
  • Beach GA, Habib MR, El Hiani Y, Miller MW, Croll RP (2019) Localization of keyhole limpet hemocyanin-like immunoreactivity in the nervous system of Biomphalaria alexandrina. J Neurosci Res. 2019 Nov;97(11):1469-1482. doi: 10.1002/jnr.24497. Epub 2019 Aug 4. PMID: 31379045
  • Vaasjo LO, Quintana AM, Habib MR, Mendez de Jesus PA, Croll RP, Miller MW (2018) GABA-like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase-like immunoreactivity in the feeding motor systems of panpulmonate snails. J Comp Neurol. 2018 Aug 1;526(11):1790-1805. PMID: 29633264
  • Brown JW, Schaub BM, Klusas BL, Tran AX, Duman AJ, Haney SJ, Boris AC, Flanagan MP, Delgado N, Torres G, Rolón-Martínez S, Vaasjo LO, Miller MW, Gillette R. (2018) A role for dopamine in the peripheral sensory processing of a gastropod mollusc. PLoS One. 2018 Dec 26;13(12):e0208891. doi: 10.1371/journal.pone.0208891. eCollection 2018. PMID: 30586424
  • Mansour TA, Habib MR, Rodríguez LCV, Vázquez AH, Alers JM, Ghezzi A, Croll RP, Brown CT, Miller MW. (2017) Central nervous system transcriptome of Biomphalaria alexandrina, an intermediate host for schistosomiasis. MC Res Notes. 2017 Dec 11;10(1):729. doi: 10.1186/s13104-017-3018-6. PMID: 29228974
  • Vaasjo LO, Quintana AM, Habib MR, Mendez de Jesus PA, Croll RP, Miller MW. (2018) GABA-like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase-like immunoreactivity in the feeding motor systems of panpulmonate snails. J Comp Neurol. 2018 Aug 1;526(11):1790-1805. PMID: 29633264
  • Habib MR, Mohamed AH, Osman GY, Sharaf El-Din AT, Mossalem HS, Delgado N*, Torres G*, Rolón-Martínez S*, Miller MW, Croll RP (2015) Histamine immunoreactive elements in the central and peripheral nervous systems of the snail, Biomphalaria spp., intermediate host for Schistosoma mansoni. PLoS One, 10(6):e0129800.
  • Vallejo D, Habib MR, Delgado N*, Vaasjo LO, Croll RP, Miller MW (2014) Localization of tyrosine hydroxylase-like immunoreactivity in the nervous systems of Biomphalaria glabrata and Biomphalaria alexandrina, intermediate hosts for schistosomiasis. J Comp Neurol. 522(11):2532-52.
  • Delgado N, Vallejo D, Miller MW (2012) Localization of serotonin in the nervous system of Biomphalaria glabrata, an intermediate host for schistosomiasis. J Comp Neurol doi: 10.1002/cne.23095. [Epub ahead of print]
  • García-Crescioni K, Miller MW (2011) Revisiting the reticulum: feedforward and feedback contributions to motor program parameters in the crab cardiac ganglion microcircuit. J Neurophysiol 106(4):2065-2077.
  • Martínez-Ruvio C, Serrano GE, Miller MW (2010) Octopamine promotes rhythmicity but not synchrony in a bilateral pair of bursting motor neurons in the feeding circuit of Aplysia. J Exp Biol 213(Pt 7):1182-1194.
  • García-Crescioni K, Fort TJ, Stern E, Brezina V, Miller MW (2010) Feedback from peripheral musculature to central pattern generator in the neurogenic heart of the crab Callinectes sapidus: role of mechanosensitive dendrites. J Neurophys 103(1):83-96.
  • Martínez-Rubio C, Serrano GE, Miller MW (2009) Localization of biogenic amines in the foregut of Aplysia californica: catecholaminergic and serotonergic innervation. J Comp Neurol. 514:329-42.
  • Miller MW (2008) Colocalization and cotransmission of classical neurotransmitters: an invertebrate perspective. In: Co-existence and Co-release of Classical Neurotransmitters (R. Gutiérrez, Ed.) Springer. New York.
  • Stern E, Fort T, Miller M, Peskin C, Brezina V (2007) Decoding modulation of the neuromuscular transform.  Neurocomputing 70: 1753-1758.
  • Fort TJ, García Crescioni K, Agricola H-J, Brezina V, Miller MW (2007) Regulation of the crab heartbeat by crustacean cardioactive peptide (CCAP): Central and peripheral actions.  J. Neurophysiology. 97: 3407-3420.
  • Serrano GE, Martínez-Rubio C, Miller MW (2007) Endogenous motor neuron properties contribute to a program-specific phase of activity in the polymorphic feeding central pattern generator of Aplysia. J. Neurophysiology. 98: 29-42.
  • Fort TJ, Brezina V, Miller MW (2007) Regulation of the crab heartbeat by FMRFamide-Like peptides: Multiple interacting effects on center and periphery. J. Neurophysiology 98: 2007-2902.
  • Serrano GE, Miller MW (2006) Conditional rhythmicity and synchrony in a bilateral pair of bursting motor neurons in AplysiaJ. Neurophysiology 96:2057-2071.
  • McPhie DL, Miller MW (2006) Biological Bulletin virtual symposium: Marine invertebrate models of learning and memory. Biological Bulletin 210: 171-173.
  • Díaz-Ríos M, Miller MW (2006) Target-specific regulation of synaptic efficacy in the feeding central pattern generator of Aplysia: Potential substrates for behavioral plasticity? Biological Bulletin 210: 215-229.
  • Díaz-Ríos M, Miller MW (2005) Rapid dopaminergic signaling by interneurons that contain markers for catecholamines and GABA in the feeding circuitry of Aplysia. J Neurophysiol. 93: 2142-2156.
  • Walters ET, Bodnarova M, Billy AJ, Dulin MF, Díaz-Ríos M, Miller MW, Moroz LL (2004) UCSomatotopic organization and functional properties of mechanosensory neurons expressing sensorin-A in Aplysia californica. .  J. Comparative Neurology 471: 219-240.
  • Painter SD, Cummins SF, Nichols AE, Akalal D-B G, Schein CH, Braun W, Smith JS, Susswein AJ, Levy M, de Boer PACM, ter Maat A, Miller MW, Scanlan C, Milberg RM, Sweedler JV, Nagle GT (2004) Structural and functional analysis of Aplysia attractins, a family of water-borne protein pheromones with interspecific attractiveness. Proc Natl Acad Sci 101: 6929-6933.
  • Fort TJ, Brezina V, Miller MW (2004) Modulation of an integrated central pattern generator – effector system: Dopaminergic regulation of cardiac activity in the blue crab Callinectes sapidus. J. Neurophysiol. 92: 3455-3470.
  • Robie A, Díaz-Ríos M, Miller MW (2003) A population of pedal-buccal projection neurons associated with appetitive components of Aplysia feeding behavior.  J Comp Physiol A 189: 231-244.
  • Wu JS, Jing J, Díaz-Ríos M, Miller MW, Kupfermann I, Weiss KR (2003) Identification of a GABA-containing cerebral-buccal interneuron-11 in Aplysia californicaNeurosci Letters 341:5-8.
  • Díaz-Ríos M, Oyola E, Miller MW (2002) Colocalization of GABA-like immunoreactivity and catecholamines in the feeding network of Aplysia californica.  J. Comparative Neurology 445: 29-46.
  • Kirk MD, Meyer JS, Miller MW, Govind CK (2001) Dichotomy in phasic-tonic neuromuscular structure of crayfish inhibitory axons.  J. Comparative Neurology 435: 283-290.
  • Rosen SC, Miller MW, Cropper EC, Kupfermann I (2000) Outputs of radula mechanoafferent neurons in Aplysia are modulated by motor neurons, interneurons, and sensory neurons.  J. Neurophysiology 83:1621-36.
  • Rosen SC, Miller MW, Evans CG, Cropper EC, Kupfermann I (2000) Diverse synaptic connections between peptidergic radula mechanoafferent neurons and neurons in the feeding system of AplysiaJ. Neurophysiology 83:1605-20.
  • Delgado JY, Oyola E, Miller MW (2000) Localization of GABA- and glutamate-like immunoreactivity in the cardiac ganglion of the spiny lobster Panulirus argusJ. Neurocytology 29: 605-619.
  • Díaz-Ríos M, Suess E, Miller MW (1999) Localization of GABA-like immunoreactivity in the central nervous system of Aplysia californicaJ. Comparative Neurology 413: 255-270.
  • Alexeeva V, Borovikov D, Miller MW, Rosen SC, Cropper EC (1998) Effect of a serotonergic extrinsic modulatory neuron (MCC) on radula mechanoafferent function in Aplysia. J. Neurophysiology 80: 1609-1622.
  • Miller MW (1997) A cellular approach to the study of complex natural behavior patterns in the ragged sea hare (Bursatella leachii), a marine invertebrate indigenous to Puerto Rico.  Puerto Rico Health Sci. J. 16: 23-36.
  • Giardino ND, Aloyz RS, Zollinger M, Miller MW, DesGroseillers L (1996) The L5-67 and LUQ-1 peptide precursors of Aplysia californica: Distribution and localization of immunoreactivity in the central nervous system and in peripheral tissues.  J. Comparative Neurology 374: 230-245.
  • Ramos LJ, Rocafort JLL, Miller MW (1995) Behavior patterns of the aplysiid gastropod Bursatella leachii in its natural habitat and in the laboratory.  Neurobiol. of Learning and Memory 63: 246-259.
  • Miller MW, Rosen SC, Schissel SL, Cropper EC, Kupfermann I, Weiss KR (1994) A population of SCP-containing neurons in the buccal ganglion of Aplysia are radula mechanoafferents and receive excitation of central origin.  J. Neuroscience 14: 7008-7023.
  • Miller MW, Beushausen S, Cropper EC, Eisinger K, Stamm S, Vilim FS, Vitek A, Zajc A, Kupfermann I, Brosius J, Weiss KR (1993) The buccalin-related neuropeptides: Isolation and characterization of an Aplysia cDNA clone encoding a family of peptide cotransmitters.  J. Neuroscience 13: 3346-3357.
  • Miller MW, Beushausen S, Vitek A, Stamm S, Kupfermann I, Brosius J, Weiss KR (1993) The myomodulin-related neuropeptides:  Characterization of a gene encoding a family of peptide cotransmitters in AplysiaJ. Neuroscience 13: 3358-3367.
  • Miller MW, Alevizos A, Cropper EC, Kupfermann I, Weiss KR (1992) Distribution of buccalin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californicaJ. Comparative Neurology 320: 182-195.
  • Weiss KR, Brezina V, Cropper EC, Hooper SL, Miller MW, Probst WC, Vilim FS, Kupfermann I (1992) Peptidergic co-transmission in Aplysia:  Functional implications for rhythmic behaviors.  Experientia 48: 457-463.
  • Miller MW, Vu E, Krasne FB (1992) Cholinergic transmission at the first synapse mediating the crayfish lateral giant escape reaction.  J. Neurophysiol. 68: 2174-2184.
  • Miller MW, Alevizos A, Cropper EC, Vilim FS, Karagogeos D, Kupfermann I, Weiss KR (1991) Localization of myomodulin-like immunoreactivity in the central nervous system and peripheral tissues of Aplysia californicaJ. Comparative Neurololgy 314: 627-644.
  • Kupfermann I, Rosen SC, Teyke T, Miller MW, Nagahama T, Cropper EC, Hooper S, Vilim FS, Weiss KR (1991). Feeding behavior in the sea hare, Aplysia californica: a model for the neural and behavioral study of behavioral states.  In Molluscan Neurobiology, Kits, K.S., Boer, H.H., and Joose J., Eds., Royal Netherlands Academy of Arts and Sciences, Amsterdam: 12-24.
  • Rosen SC, Teyke T, Miller MW, Weiss KR, Kupfermann I (1991) Identification and characterization of cerebral-to-buccal interneurons implicated in the control of motor programs associated with feeding in AplysiaJ. Neuroscience 11: 3630-3655.
  • Cropper EC, Miller MW, Vilim FS, Tenenbaum R, Kupfermann I, Weiss KR (1990) Buccalin is present in the cholinergic motor neuron B16 of Aplysia and it exerts presynaptic inhibitory effects at the B16-ARC neuromuscular junction.  Brain Research 512: 175-179.
  • Sullivan RE, Miller MW (1990) Cholinergic activation of the lobster cardiac ganglion. J. Neurobiology 21(4): 639-650.
  • Kupfermann I, Rosen S, Teyke T, Cropper EC, Miller M, Vilim F, Weiss KR (1989) Neurobiology of behavioral states in Aplysia: Non-associative forms of plasticity of feeding responses. In: Dynamics and Plasticity in Neuronal Systems, Elsner, N., and Winger, W., Eds.; Georg Thieme Verlag, N.Y., pp. 47-59.
  • Cropper EC, Miller MW, Tenenbaum R, Kolks MAG, Kupfermann I, Weiss KR (1988) Structure and action of buccalin: A modulatory neuropeptide localized to an identified small cardioactive peptide-containing motor neuron of Aplysia californica. Proc. Natl. Acad. Sci. USA, 85: 6177-6181.
  • Mirolli M, Cooke IM, Talbott SR, Miller MW (1987) Structure and localization of synaptic complexes in the cardiac ganglion of a portunid crab. J. Neurocytology 16(1): 115-130.
  • Miller MW, Lee SC, Krasne FB (1987) Cooperativity-dependent long-lasting potentiation in the crayfish lateral giant escape reaction circuit.  J. Neuroscience 7(4): 1081-1092.
  • Miller MW, Parnas H, Parnas I (1985) Dopaminergic modulation of crustacean neuromuscular transmission.  J. Physiology (London) 363: 363-375.
  • Sullivan RE, Miller MW (1984) Dual effects of proctolin on the rhythmic burst activity of the cardiac ganglion.  J. Neurobiology 15: 173-196.
  • Miller MW, Benson JA, Berlind A (1983) Effects of dopamine on the cardiac ganglia of the crabs Portunus sanguinolentus and Podopthalmus vigil.  J. Experimental Biology 108: 97-118.
  • Miller MW, Sullivan RE (1981) Some effects of proctolin on the cardiac ganglion of the Maine lobster, Homarus americanus (Milne Edwards).  J. Neurobiology 12: 629-639.