A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.

Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.

Lucifer Yellow filling of area X-projecting neurons in the high vocal center of female canaries.

The avian high vocal center (HVC) is a complex forebrain nucleus that coordinates the sensorimotor integration necessary for song learning and production. It receives auditory and potentially somatosensory input, and sends major projections to vocal motor and anterior forebrain nuclei. The HVC has at least four morphological classes of neurons for which the connectivity remains uncertain. Previous studies have alluded to the functional identity of the cell classes, but none have provided the definitive evidence necessary for subsequent identification of behaviorally relevant changes within known neuronal populations. The cell filling technique we have adapted for use in the song system provides a method by which hodologically identified classes can be described with precision, and song related changes in their morphology can be readily identified. Neurons in female canaries (Serinus canarius) that project to Area X of the anterior forebrain pathway were retrogradely labeled, selectively filled with Lucifer Yellow in a fixed slice preparation, and converted to a Golgi-like stain through an immunocytochemical reaction. We have identified Area X-projecting neurons as belonging to the thick dendrite class of Nixdorf et al. [B.E. Nixdorf, S.S. Davis, T.J. DeVoogd, Morphology of golgi-impregnated neurons in hyperstriatum ventralis, pars caudalis in adult male and female canaries, J. Comp. Neurol. 284 (1989) 337-349] and have shown definitively that they are among the HVC neurons that can receive direct auditory input, as this cell class has short dendrites that extend into the shelf region ventral to HVC that is known to receive auditory inputs. Well-filled axons had collaterals that ramified and terminated within the nucleus, demonstrating a network through which Area X-projecting cells can contribute to intrinsic HVC communication.

Memory suppressor genes: enhancing the relationship between synaptic plasticity and memory storage.

Memory suppressor genes encode proteins that act as inhibitory constraints to impede memory storage. The study of memory suppressor genes is important not only for understanding the link between synaptic plasticity and learning but also for identifying potential targets for future pharmaceuticals to treat memory disorders. This article first reviews the evidence for proteins that impede memory storage from work in invertebrates and then explores recent evidence for the existence of memory suppressor genes in vertebrates in the context of hippocampus-dependent forms of memory. In Aplysia, memory suppressor gene products act at each step in long-term facilitation: in the cytoplasm to regulate kinase activity, in the nucleus to alter the activity of transcriptional regulatory proteins, and on the cell surface to modulate cell-cell interactions. Studies of genetically modified Drosophila have provided behavioral evidence for the existence of memory suppressor genes. One of the best candidates for a neuronal mechanism underlying learning is long-term potentiation (LTP), which has been extensively studied in the mammalian hippocampus. Recent work has identified a number of putative memory suppressor gene products that act in the hippocampus at the levels of LTP induction, regulation of intracellular signaling cascades, and transcriptional control. Using these gene products as tools to study enhancements rather than deficits in LTP and learning may generate more precise information about the relationship between synaptic plasticity and behavioral learning. The study of mammalian memory suppressor genes may provide insights into alleviating the learning and memory deficits that accompany both normal aging and a variety of human disorders.

The acute and chronic toxicity of ammonia to marine fish and a mysid.

The acute toxicity (96-hr LC50) of un-ionized ammonia to mysids (Mysidopsis bahia) and larval inland silversides (Menidia beryllina) was influenced by pH and salinity in a species specific manner. With mysids, NH3 was most toxic at pH 7.0 and less toxic at pH 8.0 and 9.0. In contrast, NH3 toxicity to inland silversides was greatest at pH 7.0 and 9.0 and lowest at pH 8.0. A drop in salinity from 31 g/kg to 11 g/kg uniformly increased toxicity to mysids over this pH range. In contrast, in silversides at 11 g/kg, NH3 toxicity was less at pH 7.0, greater at pH 8, and slightly less at pH 9, relative to the toxicity at 31 g/kg. Temperature had no significant effect on the acute toxicity of un-ionized ammonia with acclimated mysids tested at 18, 25 and 32.5 degrees C, but did have a small effect with acclimated larval sheepshead minnows (Cyprinodon variegatus) tested at 13, 25 and 32.5 degrees C. The chronic toxicity value (the geometric mean of the highest no-effect concentration and lowest effect concentration) at pH 8.0, 25 degrees C and 31 g/kg salinity is 0.061 mg NH3/L for inland silversides and 0.232 mg NH3/L for mysids; the acute:chronic ratio is 21.3 and 7.2, respectively.