Nicholas Wall

All Publications

• Brain-Wide Activity Mapping Reveals a Required Role for the Dorsal Endopiriform Nucleus in MDMA-Evoked Prosocial Behavior Heifets, B., Rijsketic, D., Salgado, J., Wall, N., Ramirez-Ovalle, G., Llorach, P., Lopez, R., Casey, A., Hietamies, T., Rastegar, Z., Barbosa, D., Beier, K., Malenka, R. ELSEVIER SCIENCE INC. 2023: S57-S58

  View details for Web of Science ID 000993018500139

• Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine. Neuron Wall, N. R., Neumann, P. A., Beier, K. T., Mokhtari, A. K., Luo, L. n., Malenka, R. C. 2019

  Abstract

  Drugs of abuse elicit powerful experiences that engage populations of neurons broadly distributed throughout the brain. To determine how synaptic connectivity is organized to enable robust communication between populations of drug-activated neurons, we developed a complementary targeting system for monosynaptic rabies virus (RV) tracing that identifies direct inputs to activated versus nonactivated neuronal populations. Analysis of over 100,000 synaptic input neurons demonstrated that cocaine-activated neurons comprise selectively connected but broadly distributed corticostriatal networks. Electrophysiological assays using optogenetics to stimulate activated versus nonactivated inputs revealed stronger synapses between coactivated cortical pyramidal neurons and neurons in the dorsal striatum (DS). Repeated cocaine exposure further enhanced the connectivity specifically between drug-activated neurons in the orbitofrontal cortex (OFC) and coactive DS neurons. Selective chemogenetic silencing of cocaine-activated OFC neurons or their terminals in the DS disrupted behavioral sensitization, demonstrating the utility of this methodology for identifying novel circuit elements that contribute to behavioral plasticity.

  View details for DOI 10.1016/j.neuron.2019.10.032

  View details for PubMedID 31759807

• Diversity of transgenic mouse models for selective targeting of midbrain dopamine neurons. Neuron Lammel, S., Steinberg, E. E., Földy, C., Wall, N. R., Beier, K., Luo, L., Malenka, R. C. 2015; 85 (2): 429-438

  Abstract

  Ventral tegmental area (VTA) dopamine (DA) neurons have been implicated in reward, aversion, salience, cognition, and several neuropsychiatric disorders. Optogenetic approaches involving transgenic Cre-driver mouse lines provide powerful tools for dissecting DA-specific functions. However, the emerging complexity of VTA circuits requires Cre-driver mouse lines that restrict transgene expression to a precisely defined cell population. Because of recent work reporting that VTA DA neurons projecting to the lateral habenula release GABA, but not DA, we performed an extensive anatomical, molecular, and functional characterization of prominent DA transgenic mouse driver lines. We find that transgenes under control of the tyrosine hydroxylase, but not the dopamine transporter, promoter exhibit dramatic non-DA cell-specific expression patterns within and around VTA nuclei. Our results demonstrate how Cre expression in unintentionally targeted cells in transgenic mouse lines can confound the interpretation of supposedly cell-type-specific experiments. This Matters Arising paper is in response to Stamatakis et al. (2013), published in Neuron. See also the Matters Arising Response paper by Stuber et al. (2015), published concurrently with this Matters Arising in Neuron.

  View details for DOI 10.1016/j.neuron.2014.12.036

  View details for PubMedID 25611513

• Diversity of transgenic mouse models for selective targeting of midbrain dopamine neurons. Neuron Lammel, S., Steinberg, E. E., Földy, C., Wall, N. R., Beier, K., Luo, L., Malenka, R. C. 2015; 85 (2): 429-438

  Abstract

  Ventral tegmental area (VTA) dopamine (DA) neurons have been implicated in reward, aversion, salience, cognition, and several neuropsychiatric disorders. Optogenetic approaches involving transgenic Cre-driver mouse lines provide powerful tools for dissecting DA-specific functions. However, the emerging complexity of VTA circuits requires Cre-driver mouse lines that restrict transgene expression to a precisely defined cell population. Because of recent work reporting that VTA DA neurons projecting to the lateral habenula release GABA, but not DA, we performed an extensive anatomical, molecular, and functional characterization of prominent DA transgenic mouse driver lines. We find that transgenes under control of the tyrosine hydroxylase, but not the dopamine transporter, promoter exhibit dramatic non-DA cell-specific expression patterns within and around VTA nuclei. Our results demonstrate how Cre expression in unintentionally targeted cells in transgenic mouse lines can confound the interpretation of supposedly cell-type-specific experiments. This Matters Arising paper is in response to Stamatakis et al. (2013), published in Neuron. See also the Matters Arising Response paper by Stuber et al. (2015), published concurrently with this Matters Arising in Neuron.

  View details for DOI 10.1016/j.neuron.2014.12.036

  View details for PubMedID 25611513

• Characterization of long descending premotor propriospinal neurons in the spinal cord. journal of neuroscience Ni, Y., Nawabi, H., Liu, X., Yang, L., Miyamichi, K., Tedeschi, A., Xu, B., Wall, N. R., Callaway, E. M., He, Z. 2014; 34 (28): 9404-9417

  Abstract

  The motor function of the spinal cord requires the computation of the local neuronal circuits within the same segments as well as the long-range coordination of different spinal levels. Implicated players in this process are the propriospinal neurons (PPNs) that project their axons across different levels of the spinal cord. However, their cellular, molecular, and functional properties remain unknown. Here we use a recombinant rabies virus-based method to label a specific type of long-projecting premotor PPNs in the mouse upper spinal cord that are monosynaptically connected to the motor neurons in the lumbar spinal cord. With a whole spinal cord imaging method, we find that these neurons are distributed along the entire length of the upper spinal cord with more in the lower thoracic levels. Among them, a subset of thoracic PPNs receive substantial numbers of sensory inputs, suggesting a function in coordinating the activity of trunk and hindlimb muscles. Although many PPNs in the cervical and thoracic spinal cord receive the synaptic inputs from corticospinal tract or serotonergic axons, limited bouton numbers suggested that these supraspinal inputs might not be major regulators of the PPNs in intact animals. Molecularly, these PPNs appear to be distinct from other known premotor interneurons, but some are derived from Chx10+ lineages. This study provides an anatomical basis for further exploring different functions of PPNs.

  View details for DOI 10.1523/JNEUROSCI.1771-14.2014

  View details for PubMedID 25009272

• Cortical representations of olfactory input by trans-synaptic tracing NATURE Miyamichi, K., Amat, F., Moussavi, F., Wang, C., Wickersham, I., Wall, N. R., Taniguchi, H., Tasic, B., Huang, Z. J., He, Z., Callaway, E. M., Horowitz, M. A., Luo, L. 2011; 472 (7342): 191-196

  Abstract

  In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.

  View details for DOI 10.1038/nature09714

  View details for Web of Science ID 000289469100036

  View details for PubMedID 21179085

  View details for PubMedCentralID PMC3073090

• Genetic dissection of an amygdala microcircuit that gates conditioned fear NATURE Haubensak, W., Kunwar, P. S., Cai, H., Ciocchi, S., Wall, N. R., Ponnusamy, R., Biag, J., Dong, H., Deisseroth, K., Callaway, E. M., Fanselow, M. S., Luethi, A., Anderson, D. J. 2010; 468 (7321): 270-U230

  Abstract

  The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ(-) neurons in CEl. Electrical silencing of PKC-δ(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.

  View details for DOI 10.1038/nature09553

  View details for Web of Science ID 000284051000044

  View details for PubMedID 21068836

  View details for PubMedCentralID PMC3597095