Basal Ganglia Responses to Electrical Stimulation of the Posterior Hypothalamic Nucleus

Electrical or chemical stimulation of the posterior hypothalamic nucleus (PH) elicits highly adaptive locomotion, demonstrating both evidence of flexibility and variety in exhibited motor behaviours. However, the neural substrates of PH stimulation elicited behavioural changes are poorly understood. The basal ganglia are postulated to be critically involved in the process of action selection in conjunction with thalamo-cortical systems. The present study examines changes in basal ganglia activities in response to the high-frequency stimulation of the PH. Under urethane anaesthesia, ensemble and single-unit recordings were obtained from the striatum (STR), globus pallidus externa (GPe), entopeduncular nucleus (EP), subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Upon PH stimulation, increases in firing rates were observed in the STR, GPe, and STN, a decrease was observed in the SNr and no changes were seen in the EP. The increase in spike rate in the STR and GPe was dependent on the stimulation intensity but not duration. Despite the differences in the direction of firing changes during PH stimulation, all examined areas including those not part of the basal ganglia demonstrated an elevated spiking rate upon stimulus train termination. Taking into account the known anatomical connections between the PH and the basal ganglia, it is hypothesized responses seen during PH stimulus trains are mediated through thalamic and cortical relays whereas the overall post-stimulus excitatory response is related to the impact of the PH on brainstem arousal systems.

A121 SILENCING ENTERIC SENSORY NEURONS ABOLISHES THE EXCITATORY EFFECT OF SERTRALINE ON VAGAL AFFERENTS

Background Two thirds of vagal afferents supplying the small intestine terminate on intrinsic primary afferent neurons (IPANs) of the enteric nervous system via intraganglionic laminar endings (IGLEs) rather than the luminal epithelium (FASEB J, 28, 3064–3074, 2014). The IPAN to IGLE connection forms a functional intramural sensory synapse within the myenteric plexus. We have recently shown (Sci Rep, 9, 14290, 2019) that the antidepressant behavioural effects of selective serotonin reuptake inhibitors (SSRIs) are dependent on the vagus nerve and that intraluminal application of the SSRIs fluoxetine and sertraline increase vagal afferent firing rate in vitro. Aims We hypothesize that the vagal afferent response to intraluminal sertraline is mediated by IPAN to IGLE sensory signaling. Methods Mesenteric nerve recordings were performed using 2–3 cm jejunal segments and attached mesentery from 6–8 weeks old male Balb/c mice. Jejunal tissue was pinned out and dissected in a petri dish of Krebs to remove excess mesentery to isolate the mesenteric nerve bundle. Multi-unit electrical activity was recorded by patch-clamp electrode using an amplifier and signal converter by sucking onto the mesenteric nerve bundle with a glass micropipette. Baseline firing was recorded for 30 mins during luminal Krebs perfusion. The vagal afferent firing response to sertraline (10 µM) was measured in the absence or presence of 5 µM of the intermediate conductance calcium-dependent (IKCa) channel opener 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DCEBIO) to the serosa to selectively silence IPANs. Dataview software (J Neuroscience Methods, 185, 151, 2009) was used to isolate single unit firing post-hoc. Vagal fibre action potentials were identified by response to CCK. Results Intraluminal sertraline decreased the mean vagal interspike interval (increased vagal firing frequency) by 29% (p = 0.008) compared to Krebs control (N = 15 fibres). In contrast, addition of luminal sertraline in the presence of DCEBIO increased mean vagal interspike interval by 48% (p = 0.0103) compared to Krebs control (N = 12 fibres). Serosal addition of the N-type Ca2+ channel blocker w-Conotoxin GVIA simultaneously with luminal sertraline increased the mean vagal interspike interval by 12% (p = 0.0282) compared to Krebs control (N = 7 fibres). Conclusions Silencing of myenteric IPANs to vagus neurotransmission blocked excitatory response of vagal afferent fibres to intraluminal sertraline. Blocking myenteric neurotransmission reduced the vagus excitatory response to sertraline by more than 50%. These results suggest that the therapeutically necessary vagus nerve stimulation by sertraline involves activation of the myenteric intramural sensory synapse. Funding Agencies NSERC, OGS

Role of laterodorsal tegmentum projections to nucleus accumbens in reward-related behaviors

The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates VTA neuronal activity, but recent anatomical evidence shows that the LDT also directly projects to nucleus accumbens (NAc). We show that the majority of LDT-NAc inputs are cholinergic, but there is also GABAergic and glutamatergic innervation; activation of LDT induces a predominantly excitatory response in the NAc. Non-selective optogenetic activation of LDT-NAc projections in rats enhances motivational drive and shifts preference to an otherwise equal reward; whereas inhibition of these projections induces the opposite. Activation of these projections also induces robust place preference. In mice, specific activation of LDT-NAc cholinergic inputs (but not glutamatergic or GABAergic) is sufficient to shift preference, increase motivation, and drive positive reinforcement in different behavioral paradigms. These results provide evidence that LDT-NAc projections play an important role in motivated behaviors and positive reinforcement, and that distinct neuronal populations differentially contribute for these behaviors.

EFEK EKSTRAK ETANOL DAUN SINGKONG (Manihot Utilissima Pohl) SEBAGAI OBAT ALTERNATIF ANTI REMATIK TERHADAP RASA SAKIT PADA MENCIT

Medicinal plants used for generations one of which is crop cassava leaves. Cassava leaves is believed to cure rheumatism, gout, anemia, constipation, and to increase endurance. This study aims to determine the Effects Of Ethanol Leaf Extract Singkong (Manihot Utilissima Pohl) As Drug Alternatif Antirheumatic Of Pain On Mice. This study was an experimental study using 25 mice. These animals were divided into five groups where each group consisted of 5 mice. Cassava leaf extracts as a control test, flamar gel as a positive control, and distilled water as a negative control. Observations were made for 45 minutes using a hot excitatory response in the form of a decrease in a lick or jump after the treatments. The results showed a decline in the response of mice to lick the feet or jump to the heat stimuli were administered after administration of cassava leaf extract. Cassava leaf extract has an effect antirheumatic to pain in mice. Based on the analysis of SPSS best dose in this study is the first dose (0.65mg / 20gr mice BB).

Gated Coupling of Dopamine and Neuropeptide Signaling Underlies Perceptual Processing of Appetitive Odors in Drosophila

How olfactory stimuli are perceived as meaningful cues for specific appetitive drives remains poorly understood. Here we show that despite their enormous diversity, Drosophila larvae can discriminatively respond to food-related odor stimuli based on both qualitative and quantitative properties. Perceptual processing of food scents takes place in a neural circuit comprising four dopamine (DA) neurons and a neuropeptide F (NPF) neuron per brain hemisphere. Furthermore, these DA neurons integrate and compress inputs from second-order olfactory neurons into one-dimensional DA signals, while the downstream NPF neuron assigns appetitive significance to limited DA outputs via a D1-type DA receptor (DoplR1)-mediated gating mechanism. Finally, Dop1R, along with a Gβ13F/Irk2-mediated inhibitory and a Gαs-mediated excitatory pathway, underlie a binary precision tuning apparatus that restricts the excitatory response of NPF neurons to DA inputs that fall within an optimum range. Our findings provide fresh molecular and cellular insights into cognitive processing of olfactory cues.

Surround suppression explained by long-range recruitment of local competition, in a columnar V1 model

Although neurons in columns of visual cortex of adult carnivores and primates share similar orientation tuning preferences, responses of nearby neurons are surprisingly sparse and temporally uncorrelated, especially in response to complex visual scenes. The mechanisms underlying this counter-intuitive combination of response properties are still unknown. Here we present a computational model of columnar visual cortex which explains experimentally observed integration of complex features across the visual field, and which is consistent with anatomical and physiological profiles of cortical excitation and inhibition. In this model, sparse local excitatory connections within columns, coupled with strong unspecific local inhibition and functionally-specific long-range excitatory connections across columns, give rise to competitive dynamics that reproduce experimental observations. Our results explain surround modulation of responses to simple and complex visual stimuli, including reduced correlation of nearby excitatory neurons, increased excitatory response selectivity, increased inhibitory selectivity, and complex orientation-tuning of surround modulation.