Dual midbrain and forebrain origins of thalamic inhibitory interneurons

Abstract

12The proportion and distribution of local inhibitory neurons (interneurons) in the thalamus 13 varies widely across mammals. This is reflected in the structure of thalamic local circuits, 14which is more complex in primates compared to smaller-brained mammals like rodents. 15An increase in the number of thalamic interneurons could arise from addition of novel 16 interneuron types or from elaboration of a plesiomorphic ontogenetic program, common to 17 all mammals. The former has been proposed for the human brain, with migration of 18 interneurons from the ventral telencephalon into higher order thalamus as one of its unique 19 features (Letinic and Rakic, 2001). 20Here, we identify a larger than expected complexity and distribution of interneurons across 21 the mouse thalamus. All thalamic interneurons can be traced back to two developmental 22 programs: one specified in the midbrain and the other in the forebrain. Interneurons migrate 23 to functionally distinct thalamic nuclei, where the midbrain-derived cells populate the sensory 24 thalamus, and forebrain-generated interneurons only the higher order regions. The latter 25 interneuron type may be homologous to the one previously considered to be human-specific, 26while we also observe that markers for the midbrain-born class are abundantly expressed in 27 the primate thalamus. These data therefore point to a shared ontogenetic organization of 28 thalamic interneurons across mammals. 29 30

Single cell plasticity and population coding stability in auditory thalamus upon associative learning

“…Using genetically-encoded Ca 2+ sensors ( Figure 1C, AAV2/5.CaMKII.GCaMP6f) (Chen et al, 2013), we tracked large populations of individual MGB neurons across a four-day auditory fear conditioning paradigm in freely moving mice. Similar to previous reports (Hackett et al, 2016), we found GABAergic fibres, typically originating in inferior colliculus and the thalamic reticular complex (Rouiller et al, 1985;Winer et al, 1996), but virtually no GABAergic somata in MGB ( Figure S1, see also Jager et al, 2019), indicating that we mainly imaged Ca 2+ activity of thalamic relay neurons. We were able to follow 97 ± 5 GCaMP6f-expressing neurons per mouse ( Figures 1D and 1E, N = 19 mice) stably within and across sessions.…”

Single-cell RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates and humans

“…Two integrated types are species-specific and likely represent neurons that were sampled from outside of dLGN, including the mouse GABA1 type (likely representing RTN neurons) and the macaque GABA2 type. The mouse GABAergic types can be roughly divided into two groups based on the expression of key transcriptional regulators (Sox14, Lef1, Otx2, Nkx2-2, and Dlx5) that reflect their developmental origin in the midbrain (Sox14+) or forebrain (Sox14-) (Scholpp and Lumsden, 2010;Jager et al, 2020). All mouse GABAergic types in dLGN and some types in the ventrolateral geniculate nucleus (LGv) and the intergeniculate leaflet (IGL) express Sox14, which is consistent with previous reports (Sellers et al, 2014;Jager et al, 2016).…”

“…5D ). Two recent studies showed that at least some of the dLGN interneuron developmental programs are conserved between primates and rodents, leading to homology in mature cell types (Golding et al, 2014; Jager et al, 2020). GABAergic neuron diversity in primate dLGN may be increased by an expanded distribution of forebrain-derived, SOX14 -negative neurons that are found predominantly in medial thalamic nuclei in mouse.…”

“…GABAergic neuron diversity in primate dLGN may be increased by an expanded distribution of forebrain-derived, SOX14 -negative neurons that are found predominantly in medial thalamic nuclei in mouse. Interestingly, this population of neurons has expanded in larger-brained primates, since SOX14 -negative neurons represent less than 10% of GABAergic cells in marmoset dLGN (Jager et al, 2020), 15% in macaque, and 40% in human.…”

LacZ‐reporter mapping ofDlx5/6expression and genoarchitectural analysis of the postnatal mouse prethalamus

“…This transmitter-related bipartition of the prethalamus recalls the subpallio-pallial partition of the neighboring telencephalon, though here no significant mixing of excitatory and inhibitory populations occurs, at least in rodents. The prethalamus also contrasts with its caudal neighbor the thalamus, where mainly glutamatergic cells are produced in rodents, with partial invasion of extrinsic inhibitory interneurons (Jager, Calpin, Durmishi, Shimogori, & Delogu, 2019;Jager et al, 2016;Jeong et al, 2011;S. Martinez & Alvarado-Mallart, 1989).…”