We use a multidisciplinary approach that combines behavioral, morphological, electrophysiological, cell biological and molecular-biological techniques to explain the neural basis of those forms of behavioral plasticity that are due to changes in the internal state of the organism. Our primary interest is in mechanisms that establish internal states and in memory mechanisms that are responsible for persistence of these states.
We have chosen to study internal states in a preparation that has a relatively simple nervous system – the marine mollusc Aplysia californica. The central nervous system of this animal is distributed into several ganglia, each of which consists of a limited number of neurons, many of which are large and easily identifiable as unique individuals.
The ability to recognize the same neurons from animal to animal has greatly facilitated the functional characterization of individual cells as sensory neurons, motor neurons and interneurons. This in turn has allowed the reconstruction of neuronal circuits that mediate a variety of behaviors. Circuit-level analysis has provided new insights into the organization of neuronal networks into mediating and modulatory systems and led to a new conceptualization of command neurons.
Studies of transmitters and modulators involved in the regulation of behavior have resulted in purification and sequencing of several novel neuropeptides and to molecular cloning of the mRNA of these molecules. These neuropeptides have now been localized to specific neurons, and shown to act as cotransmitters. To a large extent our research is now focused on the role that these peptidergic cotransmitters play in optimizing the efficiency of behavior in response to changes in the motivational state of the animal. We are particularly interested in determining:
- The relationships between different forms of behavior and the patterns of neuronal activity.
- The dependence of peptide cotransmitter release on the pattern of neuronal activity.
- The physiological consequences of the interactions between multiple cotransmitters.
- The subcellular mechanisms involved in the interaction of multiple transmitters and cotransmitters, with particular emphasis on the identification of second messengers and kinases, as well as proteins phosphorylated by these kinases.
We expect that this approach will yield a unified picture in which our understanding of behavioral plasticity will extend all the way from behavior to the molecules involved.
Jing J., Gillette R., Weiss K.R., Evolving concepts of arousal: insights from simple model systems, Rev Neurosci. (in press), 2009.
Vilim FS, Sasaki K., Rybak J, Alexeeva V, Cropper EC, Jing J, Orekhova I, Brezina V, Price D, Romanova E, Rubakhin S, Hatcher NG, Sweedler J, Weiss KR. Distinct mechanisms produce functionally complementary actions of neuropeptides that are structurally related but derived from different precursors. J Neurosc. (in press), 2009.
Sasaki K, Brezina V, Weiss KR, Jing J. Distinct inhibitory neurons exert temporally specific control over activity of a motoneuron receiving concurrent excitation and inhibition. J Neurosci. 23: 11732-11744, 2009.
Proekt A, Wong J, Zhurov Y, Kozlova N, Weiss KR, Brezina V. Predicting adaptive behavior in the environment from central nervous system dynamics. PLoS ONE 3(11): e3678, 2008.
Jing J, Vilim FS, Cropper EC, Weiss KR. Neural analog of arousal: persistent conditional activation of a feeding modulator by serotonergic initiators of locomotion J. Neurosci. 20: 12349-12361, 2008.
Sasaki K, Jing J, Due MR, Weiss KR. An input-representing interneuron regulates spike timing and thereby phase switching in a motor network. J. Neurosci. 20: 1916-1928, 2008.
Wu, JS, Due MR, Sasaki K, Proekt A, Jing J, Weiss KR. State Dependence of Spike Timing and Neuronal Function in a Motor Pattern Generating Network. J. Neurosc. 27: 10818 – 10831, 2007.
Sasaki K, Due MR, Jing J, Weiss KR. The Feeding CPG in Aplysia Directly Controls Two Distinct Outputs of a Compartmentalized Interneuron. J. Neurophysiol. 98: 3796-3801, 2007.
Jing, J. Vilim F.S, Horn, C.C, Alexeeva V, Hatcher N.G, Sasaki k, Yashina I, Zhurov Y, Kupfermann I, Sweedler JV, Weiss KR. From hunger to satiety: reconfiguration of feeding network by Aplysia neuropeptide Y. J Neurosci. 27:3490-3502, 2007.
Proekt A, Jing J, Weiss, KR. Multiple contributions of an input-representing neuron to the dynamics of the Aplysia feeding network. J Neurophysiol. 97: 3046-3056, 2007.
Koh, HY., Weiss KR. Activity-dependent peptidergic modulation of the plateau-generating neuron B64 in the feeding network of Aplysia. J Neurophysiol. 2007 97:1862-7, 2007.
Romanova, E.V., McKay, N., Weiss KR., Sweedler,. JV., Koester J. Autonomic control network active in Aplysia during locomotion includes neurons that express splice variants of R15-neuropeptides. J Neurophysiol. 97: 481-91, 2007.