Cholinergic control of striatal GABAergic microcircuits

Cholinergic interneurons (CINs) are essential elements of striatal circuits and behaviors. While acetylcholine signaling via muscarinic receptors (mAChRs) have been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on GABAergic interneurons (GINs) are equally critical. One demonstration is that CINs stimulation induces large disynaptic inhibition of SPNs mediated by nAChR activation of striatal GINs. While these circuits are ideally positioned to modulate striatal output activity, the neurons involved are not definitively identified due largely to an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs optogenetic activation evokes an intricate dual mechanism involving co-activation of pre- and postsynaptic mAChRs and nAChRs on four GINs populations. Using multi-optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs likely via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

MDN brain descending neurons coordinately activate backward and inhibit forward locomotion

Command-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming (we define ‘command-like neuron’ as a neuron whose activation elicits or ‘commands’ a specific behavior). In most animals, it remains unknown how neural circuits switch between antagonistic behaviors: via top-down activation/inhibition of antagonistic circuits or via reciprocal inhibition between antagonistic circuits. Here, we use genetic screens, intersectional genetics, circuit reconstruction by electron microscopy, and functional optogenetics to identify a bilateral pair of Drosophila larval ‘mooncrawler descending neurons’ (MDNs) with command-like ability to coordinately induce backward locomotion and block forward locomotion; the former by stimulating a backward-active premotor neuron, and the latter by disynaptic inhibition of a forward-specific premotor neuron. In contrast, direct monosynaptic reciprocal inhibition between forward and backward circuits was not observed. Thus, MDNs coordinate a transition between antagonistic larval locomotor behaviors. Interestingly, larval MDNs persist into adulthood, where they can trigger backward walking. Thus, MDNs induce backward locomotion in both limbless and limbed animals.

A command-like descending neuron that coordinately activates backward and inhibits forward locomotion

Command-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming. In most animals it remains unknown how neural circuits switch between these antagonistic behaviors: via top-down activation/inhibition of antagonistic circuits or via reciprocal inhibition between antagonistic circuits. Here we use genetic screens, intersectional genetics, circuit reconstruction by electron microscopy, and functional optogenetics to identify a bilateral pair of larval “mooncrawler descending neurons” (MDNs) with command-like ability to coordinately induce backward locomotion and block forward locomotion; the former by activating a backward-specific premotor neuron, and the latter by disynaptic inhibition of a forward-specific premotor neuron. In contrast, direct reciprocal inhibition between forward and backward circuits was not observed. Thus, MDNs coordinate a transition between antagonistic larval locomotor behaviors. Interestingly, larval MDNs persist into adulthood, where they can trigger backward walking. Thus, MDNs induce backward locomotion in both limbless and limbed animals.HighlightsMDN command-like descending neuron induces backward larval locomotionMDN neurons coordinately regulate antagonistic behaviors (forward/backward locomotion)MDN-motor circuit validated at structural (TEM) and functional (optogenetic) levelsMDN neurons induce backward locomotion in both limbless larva and limbed adult

Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleus

Neurons in the interstitial nucleus of Cajal (INC) that are known to be involved in eye and head movements are excitatory. We investigated the input-output organization of inhibitory INC neurons involved in controlling vertical saccades. Intracellular recordings were made in INC neurons activated antidromically by stimulation of the contralateral trochlear or oculomotor nucleus, and their synaptic input properties from the superior colliculi (SCs) and the contralateral INC were analyzed in anesthetized cats. Many INC neurons projected to the contralateral trochlear nucleus, Forel's field H, INC, and oculomotor nucleus, and mainly received monosynaptic excitation followed by disynaptic inhibition from the ipsi- and contralateral SCs. After sectioning the commissural connections between the SCs, these neurons received monosynaptic excitation from the ipsilateral medial SC and disynaptic inhibition via the INC from the contralateral lateral SC. Another group of INC neurons were antidromically activated from the contralateral oculomotor nucleus, INC and Forel's field H, but not from the trochlear nucleus, and received monosynaptic excitation from the ipsilateral lateral SC and disynaptic inhibition from the contralateral medial SC. The former group was considered to inhibit contralateral trochlear and inferior rectus motoneurons in upward saccades, whereas the latter was considered to inhibit contralateral superior rectus and inferior oblique motoneurons in downward saccades. The mutual inhibition existed between these two groups of INC neurons for upward saccades on one side and downward saccades on the other. This pattern of input-output organization of inhibitory INC neurons suggests that the basic neural circuits for horizontal and vertical saccades are similar.