The ability to make choices and carry out appropriate actions is critical for individual survival and well-being. Choice behaviors, from hard-wired to experience-dependent, have been observed across the animal kingdom. Although differential engagement of sensory neuronal pathways is a known mechanism, neurobiological substrates in the brain that underlie choice making downstream of sensory perception are not well understood. Here, we report a behavioral paradigm in zebrafish in which a half-light/ half-dark visual image evokes an innate choice behavior, light avoidance. Neuronal activity mapping using the immediate early gene c-fos reveals the engagement of distinct brain regions, including the medial zone of the dorsal telencephalic region (Dm) and the dorsal nucleus of the ventral telencephalic area (Vd), the teleost anatomical homologs of the mammalian amygdala and striatum, respectively. In animals that were subjected to the identical sensory stimulus but displayed little or no avoidance, strikingly, the Dm and Vd were not engaged, despite similar levels of activation in the brain nuclei involved in visual processing. Based on these findings and previous connectivity data, we propose a neural circuitry model in which the Dm serves as a brain center, the activity of which predicates this choice behavior in zebrafish.emotion | fear | anxiety | decision-making

Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2het mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2het females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2het through genetic or pharmacological manipulations targeting the GABAergic network restored gathering behaviour. We propose that pup gathering learning triggers a transient epoch of inhibitory plasticity in auditory cortex that is dysregulated in Mecp2het. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development.

Despite the potential importance that synapse regeneration plays in restoring neuronal function after spinal cord injury (SCI), even the most basic questions about the morphology of regenerated synapses remain unanswered. Therefore, we set out to gain a better understanding of central synapse regeneration by examining the number, distribution, molecular composition, and ultrastructure of regenerated synapses under conditions in which behavioral recovery from SCI was robust. To do so, we used the giant reticulospinal (RS) neurons of lamprey spinal cord because they readily regenerate, are easily identifiable, and contain large synapses that serve as a classic model for vertebrate excitatory neurotransmission. Using a combination of light and electron microscopy, we found that regenerated giant RS synapses regained the basic structures and presynaptic organization observed at control giant RS synapses at a time when behavioral recovery was nearly complete. However, several obvious differences remained. Most strikingly, regenerated giant RS axons produced very few synapses. In addition, presynaptic sites within regenerated axons were less complex, had fewer vesicles, and had smaller active zones than normal. In contrast, the densities of presynapses and docked vesicles were nearly restored to control values. Thus, robust functional recovery from SCI can occur even when the structures of regenerated synapses are sparse and small, suggesting that functional recovery is due to a more complex set of compensatory changes throughout the spinal network. J. Comp. Neurol. 518:2854–2872, 2010.

Both natural rewards and addictive substances have the ability to reinforce behaviors. It has been unclear whether identical neural pathways mediate the actions of both. In addition, little is known about these behaviors and the underlying neural mechanisms in a genetically tractable vertebrate, the zebrafish Danio rerio. Using a conditioned place preference paradigm, we demonstrate that wildtype zebrafish exhibit a robust preference for food as well as the opiate drug morphine that can be blocked by the opioid receptor antagonist naloxone. Moreover, we show that the too few mutant, which disrupts a conserved zinc finger-containing gene and exhibits a reduction of selective groups of dopaminergic and serotonergic neurons in the basal diencephalon, displays normal food preference but shows no preference for morphine. Pretreatment with dopamine receptor antagonists abolishes morphine preference in the wildtype. These studies demonstrate that zebrafish display measurable preference behavior for reward and show that the preference for natural reward and addictive drug is dissociable by a single-gene mutation that alters subregions of brain monoamine neurotransmitter systems. Future genetic analysis in zebrafish shall uncover further molecular and cellular mechanisms underlying the formation and function of neural circuitry that regulate opiate and food preference behavior.

The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof͞ Fezl) in zebrafish. However, how Tof͞Fezl regulates the commitment and differentiation of these DA neurons is not known. Proneural genes encoding basic helix-loop-helix transcription factors regulate the development of multiple neuronal lineages, but their involvement in vertebrate DA neuron determination is unclear. Here we show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish. Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the panneuronal marker Hu in nonneural ectoderm. We further show that Tof͞Fezl is required to establish basal forebrain ngn1-expressing DA progenitor domains. These findings identify Ngn1 as a determinant of brain DA neurons and provide insights into how Tof͞Fezl regulates the development of these clinically important neuronal types.neurogenin 1 ͉ pluripotent neural stem cell ͉ neurotransmitter phenotype ͉ commitment and differentiation T he determination of neurotransmitter phenotype is an important aspect of neuronal differentiation, and in this regard, dopaminergic (DA) neurons have attracted considerable attention because of their functional and medical importance (1). Degeneration of substantia nigra DA neurons in humans is a hallmark of Parkinson's disease, and the malfunction of DA neurons in other brain regions is implicated in psychiatric disorders and neuroendocrine dysregulation. Therefore, understanding the determination of DA phenotype and the specification of DA neuronal circuitry may provide mechanistic and therapeutic insights into these disorders. To date, only limited number of known or putative transcriptional regulators, including Pax6, Dlx, Nurr1, Lmx1a, Lmx1b, Msx1, Foggy, and Too Few (Tof͞Fez1), have been implicated in the specification of DA phenotype in vertebrates (2-7, 35). Despite this knowledge, the mechanisms leading to the early commitment of pluripotent neural stem cells to DA lineage remain elusive.The earliest DA neurons in zebrafish are detected at Ϸ24 h postfertilization (hpf) in the basal forebrain (8). They express tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, and dopamine transporter (DAT), a protein involved in dopamine reuptake (9). Later during development, these DA neurons have both ascending and descending projections, and are believed to be homologous to mammalian DA neurons of both the basal forebrain and midbrain (10,11).Through forward genetic analysis, an adult viable zebrafish mutant named too few (tof m808 ) has been isolated that displays selective deficits of basal forebrain DA as well as adjacent serotonergic (5HT) neurons (8). Molecular characterizations have revealed that the too few mutant carries a point mutation that changes Cys-287 t...