Prelimbic cortical targets of ventromedial thalamic projections include inhibitory interneurons and corticostriatal pyra

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ORIGINAL ARTICLE

Prelimbic cortical targets of ventromedial thalamic projections include inhibitory interneurons and corticostriatal pyramidal neurons in the rat Bianca Sieveritz1   · Gordon W. Arbuthnott1  Received: 19 September 2019 / Accepted: 28 June 2020 © The Author(s) 2020

Abstract Ventromedial thalamic axons innervate cortical layer I and make contacts onto the apical dendritic tuft of pyramidal neurons. Optical stimulation of ventromedial thalamic axon terminals in prefrontal cortical areas in mouse brain slices evokes responses in corticocortical, corticothalamic and layer I inhibitory interneurons. Using anterograde tracing techniques and immunohistochemistry in male Sprague–Dawley rats, we provide anatomical evidence that ventromedial thalamic axon terminals in prelimbic cortex make contacts onto pyramidal neurons and, in particular, onto corticostriatal neurons as well as layer I inhibitory interneurons. Using stereology, we made quantitative estimates of contacts in uppermost prelimbic layer I onto dendrites of pyramidal neurons, corticostriatal neurons and layer I inhibitory interneurons. Prefrontal cortex has long been associated with decision making. Specifically, corticostriatal neurons in rat prelimbic cortex play an important role in cost–benefit decision making. Although recent experiments have detailed the physiology of this area in thalamocortical circuits, the extent of the impact of ventromedial thalamic input on corticostriatal neurons or layer I inhibitory interneurons has not been explored. Our quantitative anatomical results provide evidence that most ventromedial thalamic input to pyramidal neurons is provided to corticostriatal neurons and that overall more contacts are made onto the population of excitatory than onto the population of inhibitory neurons. Keywords  Ventromedial thalamus · Prelimbic cortex · Inhibitory interneurons · 5HT3aR · Corticostriatal neurons · RGS14

Introduction Ventromedial (VM) thalamic projection neurons extensively innervate cortical layer I (Herkenham 1979; Arbuthnott et al. 1990). Biane et al. (2016) optically stimulated axon terminals from the ventral motor thalamic nuclei, i.e., the ventromedial, ventrolateral and ventral anterior thalamic nuclei (Sieveritz et al. 2019), and recorded monosynaptic responses ex-vivo in rat primary motor cortex. After skilled grasp training, response amplitude of layer V neurons that control grasp related muscles in the distal forelimb was significantly larger compared to layer V neurons that control muscles in the proximal forelimb (Biane et al. 2016). Given that these * Bianca Sieveritz [email protected]; bsieveri@uni‑osnabrueck.de 1



Okinawa Institute of Science and Technology Graduate University, 1919‑1 Tancha, Onna‑son, Okinawa 904‑0495, Japan

neurons are targets of ventral motor thalamic projection neurons their axons may be involved in memory formation, a prerequisite for many behavioral tasks. In mice, VM projection neurons to a cortical region named anterior lateral motor cortex (ALM; from bregma AP