General Research Interests:

The Storm lab has a general interest in signaling mechanisms underlying neuroplasticity with an emphasis on the role of signal transduction crosstalk. Current interests include the molecular basis of memory formation, adaptive responses in the olfactory system and the relationship between circadian rhythm and memory consolidation. The lab uses an interdisciplinary approach to study neuroplasticity including studies of signaling mechanisms in cultured neurons, transgenic mouse model studies, electrophysiology and behavioral studies. 

I. Molecular Basis of Memory formation:

There is considerable interest in the molecular basis of memory formation. Studies of learning and memory are of fundamental importance for a better understanding of cognitive disorders in humans including Alzheimer’s, autism, aging-related memory loss, and various types of mental retardation. Long-term memory (LTM) depends on increased translation and transcription in the brain. One of the transcriptional pathways implicated in LTM and several other forms of neuroplasticity is the CRE (cAMP response element)-transcriptional pathway. We hypothesize that Ca2+ stimulation of CRE-mediated transcription plays a pivotal role for some forms of LTM. This hypothesis is supported by our data showing activation of CRE-mediated transcription and CREB phosphorylation during LTM. Furthermore, we have used CRE oligonucleotide decoys to show that contextual memory depends upon CRE-mediated transcription in the hippocampus. Transgenic mouse experiments carried out in this lab have identified calmodulin-stimulated adenylyl cyclases as key components of the signaling mechanisms required for LTM. Despite evidence supporting a role for CRE-mediated transcription in memory, this hypothesis does not readily explain the duration of LTM which can persist well beyond the lifetime of gene products increased during training for memory formation. However, we recently obtained evidence for reactivation of signaling events in the brain which may explain the persistence of LTM. Our general objectives are to study mechanisms for stimulation of CRE-mediated transcription in CNS neurons and to understand why and how increased activation of this pathway contributes to LTM.

II. Circadian Biology and Memory Formation:

The circadian organization of behavior determines how complex organisms respond to light/dark cues encountered on a daily and seasonal basis. Furthermore, there is increasing evidence that the circadian rhythm may be important for memory consolidation. Disruption of the circadian rhythm in humans can lead to sleep disorders, mental fatigue, memory defects, and depression, particularly with aging patients. Circadian rhythms are generated and controlled by an endogenous clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. Retinal light signals mediated through the retinohypothalmic tract stimulate glutamate release in the SCN and maintain time-of-day congruence between the SCN and the external environment. Although the mechanism by which light entrains the circadian cycle in the SCN is not defined it is mediated through a transcriptional cycle involving several genes including CREB, period, and timeless genes. We are studying mechanisms underlying glutamate stimulation of Per1 expression in the SCN and the contribution of this pathway to circadian behavior. We are also studying the role of the circadian rhythm in memory consolidation.

III. Molecular Basis of Long-Term Adaptive Changes in the Olfactory System:

In humans, the sense of smell is critical for protection against external hazard. Perturbations of the olfactory system cause loss of appetite and poor nutrition, particularly with older patients. For example, the average human loses a significant proportion of their olfaction as they age, and olfactory dysfunction is associated with several aging-related diseases including Alzheimer’s and Parkinson’s disease. One of the earliest clinical indicators of Parkinson’s is loss of olfaction. Olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE) are constantly insulted by exogenous stress. Furthermore, enhanced olfaction experienced by some women during pregnancy can deleteriously affect nutrition. It is estimated that there are approximately 3 million patients in the US with serious olfactory impairment. Vertebrates detect and distinguish between thousands of different odorants. For an animal to respond to odorants, olfactory signal transduction must be rapid and reversible. Furthermore, odorant exposure can lead to long-term adaptive responses in OSNs including sensitization. One of the interesting features of OSNs is that they are constantly dying and being replaced by low-level neurogenesis in the MOE. Consequently, there is considerable interest in the mechanisms that control cell survival and neurogenesis in the MOE. Our research focuses on mechanisms that mediate the detection of odorants and contribute to transcription-dependent, long-term adaptive responses in the MOE. In addition, we are studying mechanisms for pheromone detection.