A Novel Neural Substrate for the Transformation of Olfactory Inputs into Motor Output

Anatomical and physiological experiments in the lamprey reveal the neural circuit involved in transforming olfactory inputs into motor outputs, which was previously unknown in a vertebrate

The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking

How does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In male, but not female mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry in male mice during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics. Further, drinking mechanics alone from drinking session data predicted alcohol-related circuit changes. AIC→DLS manipulation did not alter operant, valence, or anxiety-related behaviors. These findings suggest that alcohol-mediated changes at AIC inputs govern behavioral sequences that maintain binge drinking and may serve as a circuit-based biomarker for the development of alcohol use disorder

Prenatal Opioid Exposure Impairs Endocannabinoid and Glutamate Transmission in the Dorsal Striatum

The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear whether prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) to examine synaptic functioning in adolescent PME offspring. PME impacted the proteome and phosphoproteome in a region- and sex-dependent manner. Many proteins and phosphorylated proteins associated with glutamate transmission were differentially abundant in PME offspring, which was associated with reduced glutamate release in the DLS and altered the rise time of excitatory events in the DMS. Similarly, the intrinsic excitability properties of DMS neurons were significantly affected by PME. Last, pathway analyses revealed an enrichment in retrograde endocannabinoid signaling in the DLS, but not in the DMS, of males. Electrophysiology studies confirmed that endocannabinoid-mediated synaptic depression was impaired in the DLS, but not DMS, of PME-males. These results indicate that PME induces persistent neuroadaptations in the dorsal striatum and could contribute to the aberrant behavioral development described in offspring with prenatal opioid exposure

Synthetic Approaches to Neurobiology: Review and Case Study in the Control of Anguiliform Locomotion

. This paper briefly reviews synthetic approaches to neurobiology and presents results of two experiments on the use of evolutionary algorithms for the design of neural controllers for locomotion. The first experiment consists in using the evolutionary algorithm for instantiating low level parameters of a connectionist simulation of the lamprey's locomotor circuitry. The second experiment develops potential neural circuits for the swimming and trotting of the salamander; an animal whose locomotor circuitry has currently not been decoded. In both cases, biologically plausible control circuits are developed which produce a neural activity with many similarities to that measured in the real animals. 1 Synthetic approaches to neurobiology The fields of artificial life and artificial intelligence have developed tools and methods which have the potential to significantly help computational neurobiology. Synthetic approaches to neurobiology can indeed increase our understanding of ..

Initiation of locomotion in lampreys

The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in the PRRN require stronger stimulation strengths. The output from the MLR on one side activates reticulospinal neurons on both sides in a highly symmetrical fashion. This could account for the symmetrical bilateral locomotor output evoked during unilateral stimulation of the MLR in all animal species tested to date. Interestingly, muscarinic receptor activation reduces sensory inputs to reticulospinal neurons and, under natural conditions, the activation of MLR cholinergic neurons will likely reduce sensory inflow. Moreover, exposing the brainstem to muscarinic agonists generates sustained recurring depolarizations in reticulospinal neurons through pre-reticular effects. Cells in the caudal half of the rhombencephalon appear to be involved and we propose that the activation of these muscarinoceptive cells could provide additional excitation to reticulospinal cells when the MLR is activated under natural conditions. One important question relates to sources of inputs to the MLR. We found that substance P excites the MLR, whereas GABA inputs tonically maintain the MLR inhibited and removal of this inhibition initiates locomotion. Other locomotor centers exist such as a region in the ventral thalamus projecting directly to reticulospinal cells. This region, referred to as the diencephalic locomotor region, receives inputs from several areas in the forebrain and is likely important for goal-directed locomotion. In summary, this review focuses on the most recent findings relative to initiation of lamprey locomotion in response to sensory and internal cues in lampreys

Spinal reflexes in the long-tailed stingray, Himantura fai

We have exploited the segregation of motor and sensory axons into peripheral nerve sub-compartments to examine spinal reflex interactions in anaesthetized stingrays. Single, supra-maximal electrical stimuli delivered to segmental sensory nerves elicited compound action potentials in the motor nerves of the stimulated segment and in rostral and caudal segmental motor nerves. Compound action potentials elicited in segmental motor nerves by single stimuli delivered to sensory nerves were increased severalfold by prior stimulation of adjacent sensory nerves. This facilitation of the segmental reflex produced by intense conditioning stimuli decreased as it was applied to more remote segments, to approximately the same degree in up to seven segments in the rostral and caudal direction. In contrast, an asymmetric response was revealed when test and conditioning stimuli were delivered to different nerves, neither of which was of the same segment as the recorded motor nerve: in this configuration, conditioning volleys generally inhibited the responses of motoneurons to stimuli delivered to more caudally located sensory nerves. This suggests that circuitry subserving trans-segmental interactions between spinal afferents is present in stingrays and that interneuronal connections attenuate the influence that subsequent activity in caudal primary afferents can have on the motor elements. © Springer, Part of Springer Science+Business Medi