A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

Physiology of electrosensory lateral line lobe neurons in Gnathonemus petersii

In mormyrid electric fish, sensory signals from electroreceptors are relayed to secondary sensory neurons in a cerebellum-like structure known as the electrosensory lateral line lobe (ELL). Efferent neurons and interneurons of the ELL also receive inputs of central origin, including electric organ corollary discharge signals, via parallel fibers and via fibers from the juxtalobar nucleus. To understand the cellular mechanisms of the integration of sensory inputs and central inputs in the ELL, the intracellular activity and ionic properties of the efferent projection neurons and interneurons were examined in an in vitro slice preparation.We focus here on the electrophysiological properties of the efferent neurons of the ELL network, the large fusiform cells and large ganglion cells, and on a class of gamma-aminobutyric acid (GABA)-ergic interneurons known as medium ganglion (MG) cells. In response to current injection through a recording pipette, both types of efferent neuron fire a large narrow spike followed by a large hyperpolarizing afterpotential. The MG cells fire a complex spike which consists of small narrow spikes and a large broad spike. Although the forms of the action potentials in efferent neurons and in MG cells are different, all spikes are mediated by tetrodotoxin (TTX)-sensitive Na+ conductances and spike repolarization is mediated by tetraethylammonium (TEA+)-sensitive K+ conductances. In the presence of TEA+, substitution of Ba2+ for Ca2+ in the bath revealed the presence of a high-voltage-activated Ca2+ conductance.Stimulation of parallel fibers conveying descending input to the ELL molecular layer in vitro evokes an excitatory postsynaptic potential (EPSP), generally followed by an inhibitory postsynaptic potential (IPSP), in the efferent neurons. In MG cells, the same stimulation evokes an EPSP, often followed by a small IPSP. Synaptic transmission at parallel fiber synapses is glutamatergic and is mediated via both N-methyl-d-aspartate (NMDA)- and (AMPA)-type glutamate receptors. The inhibitory component of the parallel fiber response is GABAergic. It is probably mediated via the stellate neurons and the MG cells, which are themselves GABAergic interneurons intrinsic to the ELL network.A hypothetical neural circuit of the intrinsic connections of the ELL, based on the known morphology of projection neurons and medium ganglion interneurons, is presented. This circuit includes an excitatory and an inhibitory submodule. The excitatory submodule is centered on a large fusiform cell and appears to relay the sensory input as a positive ‘ON’ image of an object. The inhibitory submodule is centered on a large ganglion cell and relays a negative ‘OFF’ image to the next higher level. We suggest that MG cells exert an inhibitory bias on efferent neuron types and that the ELL network output is modulated by the dynamically plastic integration of central descending signals with sensory input.

Independence and merger of thalamocortical channels within macaque monkey primary visual cortex: Anatomy of interlaminar projections

An important issue in understanding the function of primary visual cortex in the macaque monkey is how the several efferent neuron groups projecting to extrastriate cortex acquire their different response properties. To assist our understanding of this issue, we have compared the anatomical distribution of VI intrinsic relays that carry information derived from magno- (M) and parvocellular (P) divisions of the dorsal lateral geniculate nucleus between thalamic recipient neurons and interareal efferent neuron groups within area VI. We used small, iontophoretic injections of biocytin placed in individual cortical laminae of area VI to trace orthograde and retrograde inter- and intralaminar projections. In either the same or adjacent sections, the tissue was reacted for cytochrome oxidase (CO), which provides important landmarks for different efferent neuron populations located in CO rich blobs and CO poor interblobs in laminae ⅔, as well as defining clear boundaries for the populations of efferent neurons in laminae 4A and 4B. This study shows that the interblobs, but not the blobs, receive direct input from thalamic recipient 4C neurons; the interblobs receive relays from mid 4C neurons (believed to receive convergent M and P inputs), while blobs receive indirect inputs from either M or P (or both) pathways through layers 4B (which receives M relays from layer 4Cα) and 4A (which receives P relays directly from the thalamus as well as from layer 4Cβ). The property of orientation selectivity, most prominent in the interblob regions and in layer 4B, may have a common origin from oriented lateral projections made by mid 4C spiny stellate neurons. While layer 4B efferents may emphasize M characteristics and layer 4A efferents emphasize P characteristics, the dendrites of their constituent pyramidal neurons may provide anatomical access to the other channel since both blob and interblob regions in layers ⅔ have anatomical access to M and P driven relays, despite functional differences in the way these properties may be expressed in the two compartments.