Biology subjects

Paulsen, O.

Publications and source records attributed to Paulsen, O..

2 recordsLinked to original sources

bioRxiv2018

Basal forebrain and brainstem cholinergic neurons differentially impact amygdala circuits and learning-related behavior

The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in ChAT-cre mice we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous ACh release resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of acetylcholine-mediated rhythmicity in amygdala networks. Consistent with this, in vivo NBm activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic or nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons however resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Since learning and memory is supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories.

neuroscience↗

bioRxiv2018

Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output

Three-dimensional neural organoids are emerging tools with the potential for improving our understanding of human brain development and neurological disorders. Recent advances in this field have demonstrated their capacity to model neurogenesis1,2, neuronal migration and positioning3,4, and even response to sensory input5. However, it remains to be seen whether these tissues can model axon guidance dynamics and the formation of complex connectivity with functional neuronal output. Here, we have established a longterm air-liquid interface culture paradigm that leads to improved neuronal survival and allows for imaging of axon guidance. Over time, these cultures spontaneously form thick axon tracts capable of projecting over long distances. Axon bundles display various morphological behaviors including intracortical projection within and across the organoid, growth cone turning, decussation, and projection away from the organoid. Single-cell RNA-sequencing reveals the full repertoire of cortical neuronal identities, and retrograde labelling demonstrates these tract morphologies match the appropriate molecular identities, namely callosal and corticofugal neuron types. We show that these neurons are functionally mature, generate active networks within the organoid, and that extracortical projecting tracts innervate and activate mouse spinal cord-muscle explants. Muscle contractions can be evoked by stimulation of the organoid, while axotomy of the innervating tracts abolishes the muscle contraction response, demonstrating dependence on connection with the organoid. Overall, these results reveal a remarkable selforganization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and response to injury.

neuroscience↗