The evolution and comparative neurobiology of endocannabinoid signalling

CB(1)- and CB(2)-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB(1)-type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB(1)/CB(2)-type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB(1)/CB(2)-type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB(1)/CB(2)-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB(1)/CB(2)-mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids

Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness

<p>Abstract</p> <p>Background</p> <p>Previously we have found that cannabinoid treatment of zebra finches during sensorimotor stages of vocal development alters song patterns produced in adulthood. Such persistently altered behavior must be attributable to changes in physiological substrates responsible for song. We are currently working to identify the nature of such physiological changes, and to understand how they contribute to altered vocal learning. One possibility is that developmental agonist exposure results in altered expression of elements of endocannabinoid signaling systems. To test this hypothesis we have studied effects of the potent cannabinoid receptor agonist WIN55212-2 (WIN) on endocannabinoid levels and densities of CB₁immunostaining in zebra finch brain.</p> <p>Results</p> <p>We found that late postnatal WIN treatment caused a long-term global disregulation of both levels of the endocannabinoid, 2-arachidonyl glycerol (2-AG) and densities of CB₁immunostaining across brain regions, while repeated cannabinoid treatment in adults produced few long-term changes in the endogenous cannabinoid system.</p> <p>Conclusions</p> <p>Our findings indicate that the zebra finch endocannabinoid system is particularly sensitive to exogenous agonist exposure during the critical period of song learning and provide insight into susceptible brain areas.</p

CB1 Cannabinoid Receptor Activation Dose-Dependently Modulates Neuronal Activity within Caudal but not Rostral Song Control Regions of Adult Zebra Finch Telencephalon

CB1 cannabinoid receptors are distinctly expressed at high density within several regions of zebra finch telencephalon including those known to be involved in song learning (lMAN and Area X) and production (HVC and RA). Because: (1) exposure to cannabinoid agonists during developmental periods of auditory and sensory-motor song learning alters song patterns produced later in adulthood and; (2) densities of song region expression of CB1 waxes-and-wanes during song learning, it is becoming clear that CB1 receptor-mediated signaling is important to normal processes of vocal development. To better understand mechanisms involved in cannabinoid modulation of vocal behavior we have investigated the dose-response relationship between systemic cannabinoid exposure and changes in neuronal activity (as indicated by expression of the transcription factor, c- Fos) within telencephalic brain regions with established involvement in song learning and/or control. In adults we have found that low doses (0.1 mg/kg) of the cannabinoid agonist WIN-55212-2 decrease neuronal activity (as indicated by densities of c-fos-expressing nuclei) within vocal motor regions of caudal telencephalon (HVC and RA) while higher doses (3 mg/kg) stimulate activity. Both effects were reversed by pretreatment with the CB1-selective antagonist rimonabant. Interestingly, no effects of cannabinoid treatment were observed within the rostral song regions lMAN and Area X, despite distinct and dense CB1 receptor expression within these areas. Overall, our results demonstrate that, depending on dosage, CB1 agonism can both inhibit and stimulate neuronal activity within brain regions controlling adult vocal motor output, implicating involvement of multiple CB1-sensitive neuronal circuits. Originally published Psychopharmacology, Vol. 199, No. 2, Aug 200

Four-year-olds' strategic allocation of resources: Attempts to elicit reciprocation correlate negatively with spontaneous helping

Behaviour benefitting others (prosocial behaviour) can be motivated by self-interested strategic concerns as well as by genuine concern for others. Even in very young children such behaviour can be motivated by concern for others, but whether it can be strategically motivated by self-interest is currently less clear. Here, children had to distribute resources in a game in which a rich but not a poor recipient could reciprocate. From four years of age participants strategically favoured the rich recipient, but only when recipients had stated an intention to reciprocate. Six- and eight-year-olds distributed more equally. Children allocating strategically to the rich recipient were less likely to help when an adult needed assistance but was not in a position to immediately reciprocate, demonstrating consistent cross-task individual differences in the extent to which social behaviour is self- versus other-oriented even in early childhood. By four years of age children are capable of strategically allocating resources to others as a tool to advance their own self-interest

Structure of 55Sc and development of the N=34 subshell closure

The low-lying structure of $^{55}$Sc has been investigated using in-beam $\gamma$-ray spectroscopy with the $^{9}$Be($^{56}$Ti,$^{55}$Sc+$\gamma$)$X$ one-proton removal and $^{9}$Be($^{55}$Sc,$^{55}$Sc+$\gamma$)$X$ inelastic-scattering reactions at the RIKEN Radioactive Isotope Beam Factory. Transitions with energies of 572(4), 695(5), 1539(10), 1730(20), 1854(27), 2091(19), 2452(26), and 3241(39) keV are reported, and a level scheme has been constructed using $\gamma\gamma$ coincidence relationships and $\gamma$-ray relative intensities. The results are compared to large-scale shell-model calculations in the $sd$-$pf$ model space, which account for positive-parity states from proton-hole cross-shell excitations, and to it ab initio shell-model calculations from the in-medium similarity renormalization group that includes three-nucleon forces explicitly. The results of proton-removal reaction theory with the eikonal model approach were adopted to aid identification of positive-parity states in the level scheme; experimental counterparts of theoretical $1/2^{+}_{1}$ and $3/2^{+}_{1}$ states are suggested from measured decay patterns. The energy of the first $3/2^{-}$ state, which is sensitive to the neutron shell gap at the Fermi surface, was determined. The result indicates a rapid weakening of the $N=34$ subshell closure in $pf$-shell nuclei at $Z>20$, even when only a single proton occupies the $\pi f_{7/2}$ orbital

Monopole-driven shell evolution below the doubly magic nucleus Sn 132 explored with the long-lived isomer in Pd 126

A new isomer with a half-life of 23.0(8) ms has been identified at 2406 keV in Pd126 and is proposed to have a spin and parity of 10+ with a maximally aligned configuration comprising two neutron holes in the 1h11/2 orbit. In addition to an internal-decay branch through a hindered electric octupole transition, β decay from the long-lived isomer was observed to populate excited states at high spins in Ag126. The smaller energy difference between the 10+ and 7- isomers in Pd126 than in the heavier N=80 isotones can be interpreted as being ascribed to the monopole shift of the 1h11/2 neutron orbit. The effects of the monopole interaction on the evolution of single-neutron energies below Sn132 are discussed in terms of the central and tensor forces