As first author
A transient translaminar GABAergic interneuron circuit connects thalamocortical recipient layers in neonatal somatosensory cortex
*Marques-Smith, A., *Lyngholm, D., Kaufmann, A.-K., Stacey, J. A., Hoerder-Suabedissen, A., Becker, E. B. E., Wilson, M. C., Molnár, Z., Butt, S. J. B.
We discovered a transient, early developmental circuit connecting primary thalamus, L5b SST interneurons and L4 spiny stellate cells in barrel cortex. Connections between L5b SST cells and L4 spiny stellates are reciprocal and gradually disappear throughout development, relying on an activity-dependent process. Silencing or molecular perturbation of this circuit delays development of thalamic input onto L4.
*Anastasiades, P.G., *Marques-Smith, A., Lyngholm, D., Lickiss, T., Raffiq, S., Katzel, D., Miesenbock, G., Butt, S.J.B.
2016 Nature Communications
We used glutamate uncaging to map the development of glutamatergic inputs onto Nkx2-1 fast-spiking (putative PV+) and non-fast-spiking (putative SST+) interneurons across all layers of barrel cortex. We find two modes of IN developmental integration onto glutamatergic circuits: static and dynamic. Static integration obeys an early template whereby the laminar pattern of synaptic input remains constant throughout development. Dynamic integration involves early translaminar pathways that are eliminated before maturity. We also use a novel optogenetic approach to map the development of outputs for the whole Nkx2-1 population, revealing the existence of early transient translaminar GABAergic connections.
*Marques-Smith, A., *Favuzzi, E., Rico, B.
We preview a very interesting paper by Giordano Lippi at Darwin K. Berg's lab, where the authors reveal miR-101 as a synergistic master regulator of genetic programmes for constraining excitation in neural circuits. Concerted control of transcription is a critical feature in development. Without such master regulators, what plays out as a tightly orchestrated ensemble would quickly degenerate into a dangerous cacophony. Perhaps the most beautiful feature of development is how each process follows from and feeds on the last, whilst constraining and guiding the subsequent. This brings me to a review paper by Yehezkel Ben-Ari and Nicholas Spitzer, which illustrates this point convincing and eloquently.
*Anastasiades, P.G., *Marques-Smith, A., & *Butt, S.J.B.
2017 Journal of Physiology
We review techniques and good practice for mapping neural circuits using optical methods. This is a primer mainly aimed at neuroscientists not specialised in circuit mapping. We cover glutamate uncaging and optogenetics (multi- and single-photon), control experiments, analysis principles and future developments.
As second author
*del Pino, I., *Brotons-Mas, J.R., Marques-Smith, A., Marighetto, A., Frick, A., Marín, O., Rico, B.
2017 Nature Neuroscience
CCK+ interneurons are the rarest of two known types of cortical basket cell. In this paper we find that Erbb4 - a gene previously shown by the Rico and Marín labs to be important for synapse maturation in PV+ basket cells - regulates the synaptic inputs and outputs of CCK+ basket cells. By conditionally ablating expression of this gene in CCK+ interneurons, we further reveal that this poorly-understood population is important for spatial information coding.
Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican
Favuzzi, E., Marques-Smith, A., Deogracias, R., Winterflood, C.M., Sánchez-Aguilera, A., Mantoan, L., Maeso, P., Fernandes, C., Ewers, H., Rico, B.
We study Brevican, a perineuronal net (PNN) protein expressed by PV basket cells, whose expression we reveal to be activity-regulated. By probing Brevican+, Brevican- and Brevican-KO PV cells at the ultrastructural, molecular and physiological levels, we show that this PNN protein itself regulates expression of glutamate receptors and voltage-gated K+ channels critical for the iconic electrophysiological behaviour of fast-spiking cells. Full or cell-type specific KO of Brevican results in cognitive impairments in mice, suggesting PNN proteins are important for normative brain function.
Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats
McHugh, S.B., Marques-Smith, A., Li, J., Rawlins, J.N.P., Lowry, J., Conway, M., Gilmour, G., Tricklebank, M., Bannerman, D.M.
2013 European Journal of Neuroscience
Oxygen amperometry is an interesting technique for translational use, as it is widely believed to record a signal analogous to that found with BOLD, during human fMRI experiments. Here we record from rat dorsal and ventral hippocampus, as well as amygdala, during the acquisition and extinction of conditioned fear responses.
As middle author
Martínez-Garay, I., García-Moreno, F., Vasistha, N., Marques-Smith, A., Molnár, Z.
2016 Book Chapter, Prenatal and Postnatal Determinants of Development
In utero electroporation is a challenging but very powerful technique for genetic manipulation of the embryonic mammal. Part of my PhD in the Molnár and Butt labs involved setting up this technique, which I learnt from a stay in Tomomi Shimogori's lab. In this chapter, we discuss the methodology and its applications to the study of cortical development. During my PhD, I mainly applied the technique to deliver ChR2 to the thalamus at E11.5, in order to study the developing thalamocortical pathway in acute slices using patch-clamp and optogenetic stimulation. In my chapter section, I discuss the advantages - and limitations - of optogenetics for studying neural circuits, as well as its combination with in utero electroporation for probing early connectivity.
Using Optical Stimulation to Study the Developing Thalamocortical Circuit in Mouse Somatosensory Cortex (Introduction only)
2014 PhD Thesis, Merton College, University of Oxford, Department of Physiology, Anatomy and Genetics. Under supervision of Dr. Simon Butt and Professor Zoltán Molnár.
My PhD focused on the investigation of early cortical circuits, including subplate neurons, cortical interneurons and the thalamus. Although I greatly enjoyed working at the interface between development (Zoltán Molnár) and circuit electrophysiology (Simon Butt), this meant I had to cover a lot of ground for my thesis introduction. Moreover, neural development is a very wide field, ranging from investigation of molecular cues and genes for circuit wiring and cell differentiation to the functional analysis of early circuits and the study of plasticity and acquisition of sensory responses.
This was my attempt, back in 2013/2014, to integrate into a coherent body findings from all those subtopics of neural development. I cover subplate neurons, thalamocortical pathways, cortical interneurons, early network oscillations and developmental plasticity. Digesting and integrating all this information took me a long time and a lot of work. I thought it would be a shame to let that effort go to waste, so I am sharing the intro here, in case it is of use to you. I have blacked out any images for which I do not hold the copyright.