Ayelet Katzoff

Nitric Oxide and Memory

Nitric oxide (NO) is widely used in neural circuits giving rise to learning and memory. NO is an unusual neurotransmitter in its modes of release and action. Is its association with learning and memory related to its unusual properties? Reviewing the literature might allow the formulation of a general principle on how NO and memory are related. However, other than confirming that there is indeed a strong association between NO and memory, no simple rules emerge on the role of NO in learning and memory. The effects of NO are not associated with a particular stage or form of memory and are highly dependent on species, strain, and behavior or training paradigm. Nonetheless, a review does provide hints on why NO is associated with learning and memory. Unlike transmitters acting via receptors expressed only in neurons designed to respond to the transmitter, NO is a promiscuous signal that can affect a wide variety of neurons, via many molecular mechanisms. In circuits giving rise to learning and memory, it may be useful to signal some events via a promiscuous messenger having widespread effects. However, each circuit will use the promiscuous signal in a different way, to achieve different ends.

Astrocyte activation by Sindbis virus: Expression of GFAP, cytokines, and adhesion molecules

Sindbis virus (SV) is a member of the alphaviruses which has served as a model system for studying viral encephalitis. Although astrocytes are reported to be involved in the pathogenesis of various virus‐related diseases, the effects of SV on astrocyte function have not been reported. In this study we compared the effects of two strains of SV, SVA, and SVNI, which differ in their neurovirulent properties, on astrocytes with the use of cultured mouse astrocytes and the rat C6 glial cell line. We found that although both strains can similarly infect and replicate in astrocytes, they induced different changes in the function of these cells. The neurovirulent strain, SVNI, induced a decrease in cell number and a marked increase in the expression of GFAP, whereas SVA did not alter these parameters. In addition, SVNI induced the secretion of the cytokines TNF‐α and IL‐6, the expression of adhesion molecules, and the production of the neurotrophic factor NGF. In contrast, SVA induced smaller increases in the secretion of IL‐6 and NGF but did not alter the secretion of TNF‐α and the expression of the adhesion molecules. Neither virus induced the secretion of IL‐2, IL‐4, IL‐10 and IFN‐γ or the expression of iNOS in the cells. These results indicate that astrocytes, similar to neurons, can serve as target cells to SV infection in the CNS. Moreover, the infection of astrocytes by SVNI leads to changes characteristic of reactive astrogliosis which may contribute to the pathogenesis of SV‐induced encephalitis by enhancing the local immune response in the CNS. Glia 19:275–285, 1997.

Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible in Aplysia

Memory that food is inedible in Aplysia arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that NO functions during training as a signal of attempts to swallow. However, it has been shown that NO may also be released in other contexts affecting feeding, raising the possibility that its role in learning is unrelated to signaling attempts to swallow. We confirmed that NO during learning signals attempts to swallow, by showing that a variety of behavioral effects on feeding of blocking or adding NO do not affect learning and memory that a food is inedible. In addition, histamine had effects similar to NO on learning that food is inedible, as expected if the transmitters are released together when animals attempt to swallow. Blocking histamine during training blocked long-term memory, and exogenous histamine substituted for attempts to swallow. NO also substituted for histamine during training. Histamine at concentrations relevant to learning activates neuron metacerebral cell (MCC). However, MCC activity is not a good monitor of attempts to swallow during training, since the neuron responds equally well to other stimuli. These findings support and extend the hypothesis that NO and histamine signal efforts to swallow during learning, acting on targets other than the MCC that specifically respond to attempts to swallow.

Nitric oxide induces aspects of egg-laying behavior in Aplysia.

SUMMARY Aplysia egg laying is a complex behavior requiring synchronized activity in many organs. Aspects of the behavior are synchronized via the direct effects of peptide bag cell neurohormones and via stimuli arising during the behavior. Stimuli synchronizing egg laying were examined by treating A. fasciata with a nitric oxide (NO) donor. NO elicited normal appetitive and consummatory behaviors leading to the deposition of cordons containing egg capsules without eggs. The sites at which NO acts were investigated. The latency to egg deposition in response to a NO donor was shorter than that in response to other stimuli, consistent with NO acting at downstream sites from those affected by the other stimuli. The NO donor does not act on neurons in the head ganglia presynaptic to the bag cells or on the bag cells. Ligating the small hermaphroditic duct connecting the gonad to the accessory genital mass blocked egg laying in response to bag cell homogenates, but not in response to exogenous NO, indicating that NO does not act on the gonad. NO is released by transport of eggs along the small hermaphroditic duct, and NO directly acts on the accessory genital mass which packages eggs. NO also acts at a second site, independent of the effect on the accessory genital mass. A NO donor activates appetitive behaviors that normally precede egg laying even in A. californica that are unable to lay eggs.