PO Box 9303
108 Biomedical Road
BMRC 3rd floor
Morgantown, WV 26506
I have two main research goals. My first goal is to understand the neural mechanisms that underlie hearing. I work primarily with the inferior colliculus, the midbrain nucleus that forms the “hub” of the central auditory pathway, and is thought to be where the recognition of auditory objects is initiated. We are determining the role of ion channels and local circuitry in the inferior colliculus in differentiating between simple and complex sounds. For example, sounds such as mouse pup vocalizations, which contain a restricted subset of sound frequencies, are coded by microcircuits distinct from adult vocalizations, which are more complex interplays between sound frequency and intensity. In addition to normal auditory function, I study the role of neural circuitry in early-onset hearing loss and tinnitus. Both these hearing disorders are accompanied by changes in the sound frequency profile in central auditory nuclei.
My second goal is to elucidate how activity in neural circuits contributes to neurodegenerative disorders. Using the auditory system as well as brainstem motor nuclei, I am examining how exposure to a neurodegenerative trigger progresses from an initial alteration in signaling within specific cell types to eventual changes in large scale neural circuits, leading to progressive pathology and dysfunction of the system. We have found that glial cell pathology leads to alteration in rhythmic neuronal circuits/central pattern generators, leading to loss of specific neuronal cell types that have an intrinsically low ability to buffer internal calcium. I am examining avenues for rescue of the neurodegenerative phenotype by regulating calcium signaling in specific neuronal sub-types and restoring normal rhythmic circuit activity.
We use electrophysiological techniques, including patch-clamp, sharp microelectrode and extracellular recordings, to measure neural activity in brain slices and in vivo from awake animals, and calcium- and voltage-sensitive dyes and optogenetic manipulations to record circuit behavior.
- Sivaramakrishnan S*, Brandebura A*, Holcomb P, Heller D, Kolson D, Jackson D, Mathers P, Spirou G (2019) Perinatal Development of the Medial Nucleus of the Trapezoid Body. In The Oxford Handbook of the Auditory Brainstem; Ed. Karl Kandler; Oxford University Press. *co-first authors.
- Zuo H, Lei D, Sivaramakrishnan S, Howie B, Mulvany J, Bao J (2017) An operant-based detection method for inferring tinnitus in mice. J Neurosci Methods. Nov 1;291:227-237.
- Sivaramakrishnan S, Lynch WP (2017) Rebound from inhibition: self-correction against neurodegeneration? J Clin Cell Immunol 8:492.
- Grimsley CA, Green DB, Sivaramakrishnan S(2016). L-type calcium channels refine the population code of sound level. J Neurophysiology. Dec 1;116(6):2550-2563. Highlighted on social media.
- Li Y, Davey R, Sivaramakrishnan S*, Lynch, WP* (2014). Post-inhibitory rebound neurons and rhythmic networks are disrupted in retrovirus-induced spongiform neurodegeneration. J Neurophysiology,112:683-704. *Equal contribution as heads of laboratories.
- Grimsley CA, Sivaramakrishnan S (2014). Postnatal developmental changes in the medial nucleus of the trapezoid body in a mouse model of auditory pathology. Neuroscience Letters. 559: 152-157.
- Grimsley CA, Sanchez JT, Sivaramakrishnan S (2013).Midbrain local circuits shape sound intensity codes. Front Neural Circuits. 7:174.
- Sivaramakrishnan S, Sanchez JT, Grimsley CA (2013).High concentrations of divalent cations isolate monosynaptic inputs from local circuits in the auditory midbrain. Front Neural Circuits. 7:175.
- Chandrasekaran L, Xiao Y, Sivaramakrishnan S (2013).Functional architecture of the inferior colliculus revealed with voltage-sensitive dyes. Front Neural Circuits. 7: 41. F1000-Prime Recommended.
- Gaier E, Rodriguiz R, Ma X-M, Sivaramakrishnan S, Bousquet-Moore D, Wetsel WC, Eipper E, Mains R (2010).Neuronal responses to lemniscal stimulation in laminar brain slices of the inferior colliculus. J Assoc Res Otolaryngol. 2006 Mar 7(1):1-14.
- Sivaramakrishnan S, Sterbing-D’Angelo SJ, Filipovic B, D’Angelo WR, Oliver DL, Kuwada S (2004). GABA(A) synapses shape neuronal responses to sound intensity in the inferior colliculus. J Neuroscience 24(21):5031-5043.
- Sivaramakrishnan S, Oliver DL (2001)Distinct K currents results in physiologically disctinct cell types in the inferior colliculus of the rat. J Neuroscience, Vol 21(8):2861-2877.