Thesis: "Modulation of the stretch feedback pathway in the cardiac neuromuscular system of the American lobster, Homarus americanus."
Abstract:
The cardiac ganglion (CG) is a central pattern generator, a neural network that, when activated, produces patterned motor outputs such as breathing and walking. The CG induces the heart contractions of the American lobster, Homarus americanus, making the lobster heart neurogenic. In the American lobster, the CG is made up of nine neurons: four premotor pacemaker neurons that send signals to five motor neurons, causing bursts of action potentials from the motor neurons. These bursts cause cardiac muscle contractions that vary in strength based on the burst duration, frequency, and pattern.
The activity of the CG is modulated by feedback pathways and neuromodulators, allowing for flexibility in the CG’s motor output and appropriate responses to changes in the animal’s environment. Two feedback pathways modulate the CG motor output, the excitatory cardiac muscle stretch and inhibitory nitric oxide feedback pathways. Despite our knowledge of the modulation of the CG by feedback pathways and neuromodulators separately, little is known about how neuromodulators influence the sensory feedback response to cardiac muscle stretch. I found one neuromodulator to modulate each phase of the stretch response differently, one neuromodulator to generally not affect the stretch response, and three neuromodulators to suppress the stretch response. These results suggest neuromodulators can act to produce flexibility in a CPG’s motor output, allowing the system to respond appropriately to changes in an organism’s environment, and allow for variation in CPG responses to different stimuli.
Most memorable neuroscience course: Neurophysiology with Dan Powell
Since graduating: I am working as a Research Associate in the Nagel lab at NYU! I am currently working on a project focused on how premotor neurons regulate locomotor statistics in walking Drosophila. I’ve had a lot of fun learning about the different projects in the lab and getting exposed to all the cool science that can happen at such a big institution! I am planning to attend a Neuroscience PhD program after my time at NYU.
Thesis: "Neural compensation in response to salinity perturbation in the cardiac ganglion of the American lobster, Homarus americanus."
Abstract:
Central pattern generator (CPG) networks produce the rhythmic motor patterns that underlie critical behaviors such as breathing, walking, and heartbeat. The fidelity of these neural circuits in response to fluctuations in environmental conditions is essential for organismal survival. The specific ion channel profile of a neuron dictates its electrophysiological phenotype and is under homeostatic control, as channel proteins are constantly turning over in the membrane in response to internal and external stimuli. Neuronal function depends on ion channels and biophysical processes that are sensitive to external variables such as temperature, pH, and salinity. Nonetheless, the nervous system of the American lobster (Homarus americanus) is robust to global perturbations in these variables.
The cardiac ganglion (CG), the CPG that controls the rhythmic activation of the heart in the lobster, has been shown to maintain function across a relatively wide, ecologically-relevant range of saline concentrations in the short-term. This study investigates whether individual neurons of the CG sense and compensate for long-term changes in extracellular ion concentration by controlling their ion channel mRNA abundances. To do this, I bathed the isolated CG in either 0.75x, 1.5x, or 1x (physiological) saline concentrations for 24 h. I then dissected out individual CG motor neurons, the pacemaker neurons, and sections of axonal projections and used single-cell RT-qPCR to measure relative mRNA abundances of several species of ion channels in these cells.
I found that the CG maintained stable output with 24 h exposure to altered saline concentrations (0.75x and 1.5x), and that this stability may indeed be enabled by changes in mRNA abundances and correlated channel relationships.
Most memorable neuroscience course: Neurophysiology with Dan Powell
Since graduating: I am currently a US-UK Fulbright Postgraduate at Cardiff University in Wales, where I am studying sex-specific phenotypes in chronic kidney disease using a patient-derived model of kidney epithelial cells. I plan to pursue a career as a physician-scientist.
Thesis: "Characterizing the Motor Activity Patterns of the Mammalian Thoracic Spinal Cord Neural Network."
Abstract:
Vertebrate motor control employs neural circuitry to activate muscles within the forelimb, hindlimb, and axial regions of the body. Within the cervical and lumbar regions of the mammalian spinal cord, central pattern generator (CPG) networks produce rhythmic activity that governs forelimb and hindlimb locomotion, respectively. Between these limb-controlling segments, thoracic spinal nerves innervate trunk muscles and organs critical for everyday function. However, investigation of the rhythmic capabilities of the thoracic network is limited. Current literature generally consigns the thoracic network to serving as a connective synaptic highway between limb CPGs, leaving questions regarding its intrinsic rhythmogenic abilities unanswered. To characterize the rhythmic capabilities and investigate the structural organization of thoracic neural circuitry, spinal cords from postnatal mice (P1-P6) were extracted. Spinal preparations were maintained as full thoracolumbar cords or isolated thoracic preparations (transected at T2 and T12). Motor activity recordings were obtained extracellularly from thoracic or lumbar (L2/L5) ventral roots. To assess the effects of neuromodulation on thoracic motor rhythms, pharmacological experiments using serotonin (5-HT), NMDA, or dopamine were conducted. To explore thoracic network organization, glutamatergic receptor antagonists, APV and CNQX, were introduced. The present study determined that the thoracic spinal network can produce and sustain its own distinct rhythmic motor activity patterns once released from lumbar entrainment that seem to correspond to trunk motor and autonomic behaviors. Preliminary findings suggest that contralateral synchronization, typical of thoracic rhythms, is mediated by excitatory glutamatergic synapses. Elimination of glutamatergic activity revealed an underlying left-right alternating circuitry, posing intriguing evolutionary and functional questions.
Most memorable neuroscience course: Motor Systems with Manolo Díaz-Ríos
Since graduating: I am currently a research technician in the lab of Dr. Zhigang He at Boston Children’s Hospital. I am working on projects related to identifying the morphology and physiology of diverse populations of spinal projecting neurons (SPNs) and experimental spinal cord injury therapeutics aimed at promoting functional axonal regeneration. Ultimately, I plan on attending medical school or an MD-PhD program after my time at BCH.
Thesis: "The combinatorial effects of temperature and salinity on the nervous system of the American lobster, nervous system of the American lobster, Homarus americanus."
Abstract:
The ability of nervous systems to continue to function when exposed to global perturbations such as elevated temperature and altered saline concentration is a non-trivial task, and the effects of such perturbations on circuit output are impossible to predict. The nervous systems of the American lobster (H. americanus), a marine osmoconformer and poikilotherm, must be robust to these stressors as they are exposed to fluctuations in temperature on a seasonal and a daily basis, and fluctuations in salinity as rainfall patterns change and as the lobsters move between areas of the ocean that have varied depths. Using the stomatogastric nervous system (STNS) of the American lobster, I characterized the effects of temperature on the output of the pyloric circuit, a central pattern generator contained within the STNS that controls the filtration of food that the lobster consumes, and established the maximum temperature that neurons within the pyloric circuit can withstand without “crashing” (ceasing function but recovering when returned to normal conditions). I then established a range of saline concentrations that did not cause the system to crash. Lastly, I determined whether altering the saline concentration within the permissible range affected the maximum temperature that the system was able to withstand. Although burst frequency increased as temperature was increased, phase constancy was observed. The PY neurons had a greater temperature tolerance than LP in each saline concentration tested, and, interestingly, the pyloric circuit could withstand higher temperatures upon exposure to lower than normal saline concentrations. Conversely, higher saline concentrations decreased the maximum temperature tolerated by the pyloric circuit. I also established the range of saline concentrations that the lobster’s whole heart and cardiac ganglion (CG), the nervous system that controls the lobster’s heartbeat contractions, could withstand. Then, I examined whether exposure to altered saline concentrations and in conjunction with elevated temperature alters the maximum temperature that the whole heart and CG can withstand. The CG was able to withstand a wider range of saline concentrations than the whole heart without crashing and crashed at higher temperatures than the whole heart in each saline concentration. Interestingly, as observed in the STNS, the whole heart and cardiac ganglion both crashed at higher temperatures in lower saline concentrations and higher temperatures in lower saline concentrations.
Most memorable neuroscience course: Neurophysiology with Dan Powell
Since graduating: I am a neuroscience PhD student in Yale’s Interdepartmental Neuroscience program.