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    Effects of Ethanol on Sensory Inputs to the Medial Giant Interneurons of Crayfish
    (Frontiers, 2018-04-27) Swierzbinski, Matthew E.; Herberholz, Jens
    Crayfish are capable of two rapid, escape reflexes that are mediated by two pairs of giant interneurons, the lateral giants (LG) and the medial giants (MG), which respond to threats presented to the abdomen or head and thorax, respectively. The LG has been the focus of study for many decades and the role of GABAergic inhibition on the escape circuit is well-described. More recently, we demonstrated that the LG circuit is sensitive to the acute effects of ethanol and this sensitivity is likely mediated by interactions between ethanol and the GABAergic system. The MG neurons, however, which receive multi-modal sensory inputs and are located in the brain, have been less studied despite their established importance during many naturally occurring behaviors. Using a combination of electrophysiological and neuropharmacological techniques, we report here that the MG neurons are sensitive to ethanol and experience an increase in amplitudes of post-synaptic potentials following ethanol exposure. Moreover, they are affected by GABAergic mechanisms: the facilitatory effect of acute EtOH can be suppressed by pretreatment with a GABA receptor agonist whereas the inhibitory effects resulting from a GABA agonist can be occluded by ethanol exposure. Together, our findings suggest intriguing neurocellular interactions between alcohol and the crayfish GABAergic system. These results enable further exploration of potentially conserved neurochemical mechanisms underlying the interactions between alcohol and neural circuitry that controls complex behaviors.
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    Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning
    (Frontiers, 2017-02-02) Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.
    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1-/- and the M1/M3-/- knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing.
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    Response inhibition and the cortico-striatal circuit
    (2015) Bryden, Daniel William; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The ability to flexibly control or inhibit unwanted actions is critical for everyday behavior. Lack of this capacity is characteristic of numerous psychiatric diseases including attention deficit hyperactivity disorder (ADHD). My project is designed to study the neural underpinnings of response inhibition and to what extent these mechanisms are disrupted in animals with impaired impulse control. I therefore recorded single neurons from dorsal striatum, orbitofrontal cortex, and medial prefrontal cortex from rats performing a novel rodent variant of the classic "stop signal" task used in clinical settings. This task asks motivated rats to repeatedly produce simple actions to obtain rewards while needing to semi-occasionally inhibit an already initiated response. To take this a step further, I compared normal rats to rats prenatally exposed to nicotine in order to better understand the mechanism underlying inhibitory control. Rats exposed to nicotine before birth show abnormal attention, poor inhibitory control, and brain deficits consistent with impairments seen in humans prenatally exposed to nicotine and those with ADHD. I found that dorsal striatum neurons tend to encode the direction of a response and the motor refinement necessary to guide behaviors within the task rather than playing a causal role in response inhibition. However the orbitofrontal cortex, a direct afferent of dorsal striatum, possesses the capacity to inform the striatum of the correct action during response inhibition within the critical time window required to flexibly alter an initiated movement. On the other hand, medial prefrontal cortex functions as a conflict “monitor” to broadly increase preparedness for flexible response inhibition by aggregating current and past conflict history. Lastly, rat pups exposed to nicotine during gestation exhibit faster movement speeds and reduced capacity for inhibitory behavior. Physiologically, prenatal nicotine exposure manifests in a hypoactive prefrontal cortex, diminished encoding of task parameters, and reduced capacity to maintain conflict information.
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    REGULATION OF THE INHIBITORY DRIVE IN THE OLFACTORY BULB
    (2013) Nunez-Parra, Alexia Francisca; Araneda, Ricardo C; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Animals are exposed to a variety of odor cues that serve as environmental guides for their exploratory and social behaviors. Two distinct but complementing pathways process chemosensory cues: the Main and the Accessory olfactory System (AOS). Sensory neurons send their axons to the olfactory bulb (OB), specifically to the main and the accessory olfactory bulb (MOB and AOB, respectively) where they synapse onto principal neurons, the mitral (MCs). The OB is the only relay center between sensory neurons and cortical and limbic structures and therefore important aspects of odor processing occur in this region. Specifically, a distinctive mechanism used for olfactory processing is a strict regulation of MCs output by inhibitory neurons called granule cells (GCs). Importantely, inhibition of MCs is a dynamic process; it is regulated by the constant addition of new GCs to the OB circuit throughout life, in a process known as adult neurogenesis. Little is known, however, about the contribution of adult born neurons to the processing of olfactory cues, known as pheromones. Detection of pheromones by the AOS is critical for proper display of social behaviors such as hierarchical dominance and mate recognition. Here, we studied how the integration of new-born neurons could be regulated. We found that the arrival of new neurons into the adult AOB increases after animals are exposed to aggression and mate cues, suggesting that these newly arrived neurons can add important plasticity to the AOB circuitry and modify olfactory processing under different behavioral contexts. In addition, GCs mediated inhibition in the OB is precisely controlled by an extensive centrifugal innervation. For example, cortical feedback projections and neuromodulatory afferents originating in the midbrain and basal forebrain excite GC, inhibiting MCs' and decreasing their output. Regulation of of GCs by inhibition has also been reported, however, the source of this inhibition and its relevance to olfactory processing is not known. Here we characterized inhibitory inputs onto GCs and show that GCs receive extensive inhibition from GABAergic neurons in the HDB/MCPO and from neighboring GCs. Moreover, we show, for the first time, that inhibition onto GCs is required for proper olfactory discrimination.