Kumar Lab

Sanjay KumarSanjay Kumar, M.S., Ph.D.

Florida State University
College of Medicine
Dept. of Biomedical Sciences
1115 West Call Street
Tallahassee, FL 32306-4300
Dr. Kumar's Faculty Profile

Research Interests

Research in my laboratory focuses on cellular physiology of the neocortex both in the context of determining normal neocortical function as well as to gain insights into pathophysiological mechanisms underlying certain aberrant human conditions such as epilepsy.

Functional properties of excitatory synapses and underlying receptors.Basic Research
Functional properties of excitatory synapses and underlying receptors.

Deciphering cortical function is contingent on the availability of detailed information regarding underlying circuitry, its elements and more importantly its connections. Although a lot is known about the morphology and firing properties of different classes of neocortical excitatory and inhibitory neurons, information about the specific physiology of the various types of synapses, excitatory synapses in particular, has been noticeably inadequate. One goal of the laboratory is to characterize functional properties of excitatory synapses, especially on principal cells (see adjoining figure), and to correlate this information in terms of their input specificity, cell-morphology and underlying receptor (AMPA & NMDA) subunit composition and function. Another goal is to examine the generality of these observations between various regions of the neocortex and laminae and their significance both at the single cell level and in the broader context of a network. Synthesis of this information would prove instrumental in establishing the cellular basis of sensory and motor processing as well as a grass-roots level understanding of the generation and shaping of receptive fields and activity-dependent plasticity of topographic maps. Our long-term goal is to gather sufficient knowledge to be able to address such issues and eventually to determine the rules of computation within these circuits. Our general approach is outlined in the adjoining figure. [Ref: 5, 6, 7]

ResearchMechanisms of synaptic plasticity and its regulation within neocortex.

Long-lasting changes in synaptic function are generally assumed to be the cellular basis for learning and memory. This form of plasticity has been best studied in the hippocampus where it was first discovered, although it has also been reported in areas of the mammalian CNS including visual and motor cortex. However, the rules for induction, expression and maintenance of cortical long-term potentiation (LTP) are not well understood and the precise cellular mechanisms underlying these changes are still at large. Our research attempts to address these issues as a prelude to exploring the intracellular mechanisms of cortical plasticity and its modulatory regulation by endogenous amines. [Ref: 7, 8]

Laser-scanning photostimulation in layer II of medial entorhinal cortex in brain slices from control and epileptic rats uncages glutamate and evokes direct and synaptic responses.

Laser-scanning photostimulation in layer II of
medial entorhinal cortex in brain slices from
control and epileptic rats uncages glutamate and
evokes direct and synaptic responses.

Translational Research
Basic cellular mechanisms underlying cortical hyperexcitability & Temporal Lobe Epilepsy

Another note-worthy endeavor of the laboratory is to apply basic neuroscience research towards the study and understanding of clinically related pathological phenomena such as epilepsy via the identification of basic cellular mechanisms that underlie its pathophysiology. We have discovered for example that excitatory intracortical connections undergo developmental alterations in the phenotype of their receptor subunits roughly coincident with the period during which normal neocortical tissue is most epileptogenic. Although, the precise relationships between these changes and epilepsy are yet to be fully investigated, the goal of our research is to eventually provide a cellular basis for neocortical physiology related to cortical hyperexcitability and epilepsy.

Temporal Lobe Epilepsy is the most common type of epilepsy in adults, often intractable to anticonvulsant therapy and one whose pathophysiology is still poorly understood. Historically, studies of TLE have focused on the hippocampus and less attention has been given to the entorhinal cortex, a temporal lobe structure whose role in this syndrome has been recognized relatively recently. We hope to gain further insights into basic cellular mechanisms underlying TLE-related pathophysiology and epileptogenesis within the entorhinal cortex and adjoining structures using a well-defined animal model. [Ref: 2, 3]

These areas of investigation provide avenues for both graduate and undergraduate students, to train in state-of-the-art electrophysiological and anatomical techniques, participate in various on-going projects and contribute to the research effort of my laboratory.

  1. Questions addressed in this study: (1) do layer II stellate cells form recurrent excitatory synapses in control tissue? (2) do these neurons sprout axon collaterals and develop novel recurrent excitatory synapses in epileptic animals? and (3) is recurrent inhibitory synaptic input onto stellate cells from GABAergic interneurons in layer II diminished in epileptic animals?
  2. Laser-scanning photostimulation in layer II (L-II; gray area) activated stellate cells and inhibitory interneurons while responses were recorded in stellate cells. B1, Overlay of typical responses recorded in a stellate cell evoked by pseudorandom and systematic uncaging of glutamate by flash photolysis in layer II (L II). The recorded neuron in layer II medial entorhinal cortex was visualized using a microscope equipped with infrared optics (R, recording electrode). B2, Enlargement of some traces from B1 reveals four types of photostimulation-evoked responses: a, direct; b, synaptic; c, mixed; d, no response. Direct responses recorded in voltage-clamp mode (holding voltage, –70 mV) peaked within 10 ms of photostimulation. Events that peaked during a measurement window 10–30 ms after photostimulation (between blue dotted lines) were identified as potential excitatory synaptic responses.
  3. Glutamate photo-uncaging maps of direct (top) and synaptic (bottom) responses of cell shown in B. Direct responses are expressed as peak amplitudes occurring within 10 ms of photostimulation. Synaptic responses are expressed as composite EPSC amplitudes occurring 10–30 ms after photostimulation.
    Taken from Ref. 2

Laboratory Members

Denizens of the Kumar Laboratory:

Saad Abbasi (Biology)
Susan Chitwood (Biology)
Katelyn Chitwood (Biology)

Denizens of the Kumar Laboratory

Selected References

  1. Kumar SS, Buckmaster PS (2007) Neuron-specific nuclear antigen NeuN in not detectable in gerbil substantia nigra pars reticulata. Brain Res. 1142:54-60.
     
  2. Kumar SS, Jin X, Buckmaster PS, Huguenard JR (2007) Recurrent circuits in layer II of medial entorhinal cortex in a model of temporal lobe epilepsy. J. Neurosci. 27:1239-1246.
     
  3. Kumar SS, Buckmaster PS (2006) Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal cortex in a model of temporal lobe epilepsy. J. Neurosci. 26:4613-4623.
     
  4. Kumar SS, Wen X, Yang Y, Buckmaster PS (2006) GABAA receptor-mediated IPSCs and ?1 subunit expression are not reduced in the substantia nigra pars reticulata of gerbils with inherited epilepsy. J. Neurophysiol. 95:2446-2455.
     
  5. Kumar SS, Huguenard JR (2003) Pathway specific differences in subunit composition of synaptic NMDA receptors on pyramidal neurons in neocortex. J. Neurosci. 23(31):10074-10083. [Selected by the Faculty of 1000: http://www.f1000biology.com/article/14602822/ evaluation]
     
  6. Kumar SS, Bacci A, Kharazia VK, Huguenard JR (2002) A developmental switch of AMPA-receptor subunits in neocortical pyramidal neurons. J. Neurosci. 22(8):3005-3015.
     
  7. Kumar SS, Huguenard, JR (2001) Properties of excitatory synaptic connections mediated by the corpus callosum in the developing rat neocortex. J. Neurophysiol. 86(6):2973-2985.
     
  8. Kumar SS, Faber DS (1998) Plasticity of first-order sensory synapses: Interactions between homosynaptic LTP and hetrosynaptically evoked dopaminergic potentiation. J. Neurosci. 19(5):1620-1635.