Motor cortex analogue neurons in songbirds utilize Kv3 channels to generate ultranarrow spikes

Abstract

Complex motor skills in vertebrates require specialized upper motor neurons with precise action potential (AP) firing. To examine how diverse populations of upper motor neurons subserve distinct functions and the specific repertoire of ion channels involved, we conducted a thorough study of the excitability of upper motor neurons controlling somatic motor function in the zebra finch. We found that robustus arcopallialis projection neurons (RAPNs), key command neurons for song production, exhibit ultranarrow spikes and higher firing rates compared to neurons controlling non-vocal somatic motor functions (AId neurons). Pharmacological and molecular data indicate that this striking difference is associated with the higher expression in RAPNs of a high threshold, fast-activating voltage-gated K+ channel, Kv3.1 (KCNC1). The spike waveform and Kv3.1 expression in RAPNs mirror properties of Betz cells, specialized upper motor neurons involved in fine digit control in humans and other primates but absent in rodents. Our study thus provides evidence that songbirds and primates have convergently evolved the use of Kv3.1 to ensure precise, rapid AP firing in upper motor neurons controlling fast and complex motor skills.

Input and Output Connections of the Crow Nidopallium Caudolaterale

“…In combination with previous reports on the pigeon NCL, our work suggests that the NCLd is a highly integrative hub, across avian taxa. Furthermore, our data add to a diverse set of studies that have argued for a critical premotor function of the NCLd via the AID ( Yuan and Bottjer, 2020 ; Rinnert and Nieder, 2021 ; Kirschhock and Nieder, 2022 ; Zemel et al, 2023 ). The most surprising finding of our study was a dense cluster of NCLd-projecting cells at the rostral tip of the hippocampal formation.…”

“…One crucial component of the DVR is the nidopallium caudolaterale (NCL), which sits at the pallial interface of ascending, multisensory inputs and descending premotor outputs ( Kröner and Güntürkün, 1999 ; Farries, 2001 ; Fernández et al, 2020b ; Zemel et al, 2023 ). Consistent with its multimodal connectivity, the NCL plays a central role in various higher cognitive functions such as working memory ( Veit et al, 2014 ; Moll and Nieder, 2017 ), motor planning ( Rose and Colombo, 2005 ; Rinnert and Nieder, 2021 ; Kirschhock and Nieder, 2022 ; Hahn and Rose, 2023 ), prospective problem-solving ( Veit and Nieder, 2013 ; Moll and Nieder, 2015 ; Veit et al, 2015b ), magnitude estimation ( Moll and Nieder, 2014 ; Ditz and Nieder, 2015 ; Kirschhock and Nieder, 2023 ; Wagener and Nieder, 2023 ), spatial cognition ( Veit et al, 2015a ; Rinnert et al, 2019 ), or sensory consciousness ( Nieder et al, 2020 ).…”

Cell type specializations of the vocal-motor cortex in songbirds

“…The AI has diverse molecular properties and connectivity 21 , 23 , 24 , 29 , 38 including distinct electrophysiological properties of RA excitatory cells. 15 , 16 It is considered analogous to deep layers of the mammalian cortex, which has a large diversity of pyramidal cell types. 39 Accordingly, we detected several molecularly defined excitatory cells in zebra finch AI.…”

“…The difference in the inactivation properties of these channels, with Kv4.2 exhibiting profound inactivation compared to Kv2.1 and Kv2.2, 71 , 72 may in part explain the contrast in the slope of the afterhyperpolarization of APs between AI inhibitory vs. excitatory neurons. 15 , 16 , 67 , 70 Other ion channel subunit genes ( Figures S5E and S5F ) with expression unique to or enriched in inhibitory cells (e.g., CACNA1I, KCNK2/9) contrast markedly with those enriched in excitatory cells generally (e.g., KCNA10, CACNA2D4, SCN4B), in RAPNs (Excit_1) alone (e.g., KCNJ5) or in other AI excitatory cells (e.g., CACNA1H, KCNG1/3, KCNH4), but possible links to differences in AI cell excitability remain to be defined. As for inhibitory subtypes, expression of KCNN3, which encodes a small-conductance calcium-dependent potassium channel (SK3), was almost exclusive to a small proportion of cells in the Inhib_2 cluster (NPY + ; Figure S5F ), which contains the large-diameter interneurons.…”

“… 7 , 8 , 10 – 12 RA’s roles are in several ways analogous to those that corticospinal pyramidal neurons in the primate motor cortex play in the control of fine motor skills. 13 RA projection neurons are capable of firing ultrathin spikes at very high frequencies 10 , 12 , 14 due to ion channel specializations, 15 , 16 some of which are similar to those of the specialized Betz cells in the primate motor cortex, 17 and RA’s adult firing patterns result from extensive changes during the period of song learning. 14 , 15 , 18 Despite RA’s distinct physiological features and role in producing learned song, its most basic features related to cell type composition and related molecular specializations have yet to be fully defined.…”