Various transgenic mouse lines to study proopiomelanocortin cells in the brain stem label disparate populations of GABAergic and glutamatergic neurons

Products of the proopiomelanocortin (POMC) prohormone regulate aspects of analgesia, reward, and energy balance; thus, the neurons that produce POMC in the hypothalamus have received considerable attention. However, there are also cells in the nucleus of the solitary tract (NTS) that transcribe Pomc, although low levels of Pomc mRNA and relative lack of POMC peptide products in the adult mouse NTS have hindered the study of these cells. Therefore, studies of NTS POMC cells have largely relied on transgenic mouse lines. Here, we set out to determine the amino acid (AA) transmitter phenotype of NTS POMC neurons by using Pomc-Gfp transgenic mice to identify POMC cells. We found that cells expressing the green fluorescent protein (GFP) represent a mix of GABAergic and glutamatergic cells as indicated by Gad2 and vesicular Glut2 ( vGlut2) mRNA expression, respectively. We then examined the AA phenotype of POMC cells labeled by a Pomc-Cre transgene and found that these are also a mix of GABAergic and glutamatergic cells. However, the NTS cells labeled by the Gfp- and Cre-containing transgenes represented distinct populations of cells in three different Pomc-Cre mouse lines. Consistent with previous work, we were unable to reliably detect Pomc mRNA in the NTS despite clear expression in the hypothalamus. Thus, it was not possible to determine which transgenic tool most accurately identifies NTS cells that may express Pomc or release POMC peptides, although the results indicate the transgenic tools for study of these NTS neurons can label disparate populations of cells with varied AA phenotypes.

Daylight Determines Dopamine

Expression of the appropriate neurotransmitters is essential for the function of neural circuits. Can neurons change their transmitter phenotype to deal with alterations in the environment? Dulcis et al. (see the Perspective by Birren and Marder) exposed adult rats to different photoperiods mimicking summer and winter daylengths. Neurotransmitter expression switched between dopamine and somatostatin in hypothalamic neurons that regulate release of corticotropin-releasing factor. Transmitter switching occurred at the transcriptional level and was accompanied by changes in postsynaptic receptors.D. Dulcis, P. Jamshidi, S. Leutgeb, N. C. Spitzer, Neurotransmitter switching in the adult brain regulates behavior. Science340, 449–453 (2013). [Abstract][Full Text]S. J. Birren, E. Marder, Plasticity in the neurotransmitter repertoire. Science340, 436–437 (2013). [Abstract][Full Text]

Steroid-regulated morphological plasticity in a set of identified peptidergic neurons in the moth Manduca sexta

The lateral neurosecretory cells (LNCs) in the tobacco hornworm Manduca sexta undergo a switch in neurotransmitter phenotype during pupation. Concurrent with this change in function, the LNCs undergo a major morphological reorganization. This study characterizes the morphological change and its underlying cause. In the larva, the LNC has a very compact dendritic arborization in a small volume of neuropil ipsilateral to the cell soma. In the adult moth, the LNC arborization extends through a much larger volume of neuropil, including the contralateral side of the ganglion. Using both in vivo manipulations and a single-cell culture system, we show that this change in morphology is probably triggered by two pulses of the steroid hormone 20-hydroxyecdysone (20-HE): a small commitment peak and a larger prepupal pulse. These are the same two pulses of 20-HE as those previously shown jointly to cause the change in transmitter phenotype. This work, in conjunction with a previous study on the transmitter switch, documents the orchestration of major morphological and biochemical changes in a set of identified neurons by a single hormone.

Cholinergic neuronal differentiation factors: evidence for the presence of both CNTF-like and non-CNTF-like factors in developing rat footpad

Catecholaminergic sympathetic neurons are able to change their transmitter phenotype during development and to acquire cholinergic properties. Cholinergic sympathetic differentiation is only observed in fibers innervating specific targets like the sweat glands in the rat footpad. A function for ciliary neurotrophic factor (CNTF) in this process has been implied as it is able to induce cholinergic properties (ChAT, VIP) in cultured chick and rat neurons. We show here that a CNTF-like, VIP-inducing activity is present in rat footpads and that its increases 6-fold during the period of cholinergic sympathetic differentiation. Immunohistochemical analysis of P21 rat footpads demonstrated CNTF-like immunoreactivity in Schwann cells but not in sweat glands, the target tissue of cholinergic sympathetic neurons. The expression of this factor in footpads seems to be dependent on the presence of intact nerve axons, as nerve transection results in a loss of CNTF-like cholinergic activity and immunoreactivity. Immunoprecipitation experiments with rat footpad extracts provided evidence for the presence of ChAT-inducing factors other than CNTF, which may independently or together with CNTF be involved in the determination of sympathetic neuron phenotype.