Visualization of nigrosome 1 and its loss in PD: Pathoanatomical correlation and in vivo 7 T MRI.

Blazejewska AI, Schwarz ST, Pitiot A, Stephenson MC, Lowe J, Bajaj N, Bowtell RW, Auer DP, Gowland PA.
Neurology. 2013 Aug 6;81(6):534-40. PMID: 23843466
 

Objective:   Parkinson’s Disease (PD) is a progressive neurological disease marked by the loss of dopamine-producing cells in the midbrain area known as the substantia nigra (SN).  Diagnosis, and consequently therapy, usually occurs after pathognomonic motor symptoms occur, brought about by the loss of greater than 60% of the dopaminergic cells in the SN.  In this paper, diagnostic regions of the SN, known as nigrosomes, were examined by MRI in order to identify changes that could lead to earlier diagnosis of PD.

Results:

·         Areas defined by staining were able to be matched to and overlaid on MRI scans.  In the sample from the PD patient, the structure corresponding to nigrosome 1 (the area most affected by PD) could be seen on MRI, but lacked neuromelanin and staining for tyrosine hydroxylase (TH), two markers for the dopaminergic neurons in the SN.

·         The nigrosome 1 was examined in healthy volunteers with T2 weighted imaging with a 7T and a 3T scanner.  The 3T scanner could show the nigrosome, but with a lower-signal-to-noise ratio.  When compared to the nigrosome 1 of people suffering from PD, neuroradiologists blinded to the patients’ statuses could correctly classify their state of healthy in 7/8 controls and 10/10 of PD patients.

Conclusions:

·         The nigrosome 1 region of the SN can be accurately identified on a 7T MRI scanner using T2 weighted imaging.

·         Due to experimental design and small sample size, no definite conclusion can be drawn about this technique’s ability to identify PD patients before the onset of motor symptoms.  Longitudinal studies will be needed in populations being investigated for the progression of PD.

Methods:    Post-mortem human brains were acquired, formalin fixed, and imaged with a 7T MRI scanner.  The midbrains were then sectioned in to 5um slices for immunostaining.  Additional scans were done on live healthy controls and live patients with PD (diagnosed with traditional methods and shown to respond to standard therapy).  Further scans were done at 3T in order to investigate the feasibility of visualizing nigrosome 1 in a lower magnetic field.

-DH

KNOCKDOWN OF TYROSINE HYDROXYLASE IN THE NUCLEUS OF THE SOLITARY TRACT REDUCES ELEVATED BLOOD PRESSURE DURING CHRONIC INTERMITTENT HYPOXIA.

Bathina CS, Rajulapati A, Franzke M, Yamamoto K, Cunningham JT, Mifflin SW.
Am J Physiol Regul Integr Comp Physiol. 2013 Sep 18. [Epub ahead of print]. PMID: 24049117

Objective:   Sleep apnea produces chronic intermittent hypoxia (CIH) that causes elevations in sympathetic nerve activity and arterial pressure as a result of arterial chemoreceptor (CR) activation and subsequent activation of the NTS.  Since the CRs seem to preferentially activate the NTS A2 noradrenergic neurons, the role of these A2 neurons was examined by comparing the effect of CIH on wild type and tyrosine hydroxylase (TH) knockout rats.

Results:

·         Rats that had TH knocked down in the NTS with shRNA showed reduced change in MAP in the dark phase and a greater heart rate than controls.  Changes in heart rate persisted in normoxic phases in control rats, but not in knockdown rats.

·         In knockdown rats, there was a significant reduction in FosB immunoreactive cells in the PVN, but not in the controls.  This change did not significantly extend to the RVLM.

-DH

Electrical stimulation of the rostral ventrolateral medulla promotes wakefulness in rats.

Chen CY, Kuo TB, Hsieh IT, Yang CC.
Sleep Med. 2013 Aug 21. [Epub ahead of print]. PMID: 24047536

Objective:   Because people suffering from hypertension often have corresponding sleep disorders, it has been thought that the RVLM plays a role in regulating sleep activity through the regulation of blood pressure or through stimulation of other nuclei involved in wakefulness and sleep.  Indeed, the RVLM’s activity decreases during non-REM sleep, and stimulation of the RVLM during sleep causes arousal.  In this paper, the authors examine the role of RVLM activity in the transition states between wakefulness and sleep.

Results:

·         When the rats were subjected to pre-determined stimulation of the RVLM, they experienced an increase in blood pressure and in the number of transitions between active waking (AW) and non-REM sleep (NREM).  When the stimulus occurred during NREM, the rats transitioned to AW, but stimulus during REM sleep did not cause the same transition.

·         Because increases in blood pressure are sufficient to cause a NREM state animal to transition to AW, they used EEG and EMG to examine the latency between the change in wakefulness and the change in blood pressure.  They found that the brain and muscle changed activity state within 1.5 seconds, while the initial increase in blood pressure took 2.27 seconds.  This indicates that activation of the RVLM causes changes in wakefulness before it causes the changes in blood pressure.

-DH

 

Monday September 23, 2013

Glucose-Induced Cyclic AMP Oscillations Regulate Pulsatile Insulin Secretion

Oleg Dyachok, Olof Idevall-Hagren, Jenny Sa getorp, Geng Tian, Anne Wuttke, Ce´ cile Arrieumerlou, Go¨ ran Akusja¨ rvi, Erik Gylfe, and Anders Tengholm*

Cell Metabolism 8, 26–37, July 2008 ª2008 Elsevier Inc.

Background: Insulin secretion from pancreatic beta cells has been coupled with the metabolism of glucose, which has be discovered as a stimulus for insulin release. Through a specific cascade, the degradation of sugar leads to an influx of calcium into the cell and the excretion of insulin secretory granules.  All of these processes seem to happen with an orchestrated oscillation revolving around a wave like pattern of the calcium influx. Another critical messenger for insulin release is cyclic AMP, however until recently kinetics and characterization of this enzyme have been not been feasible so not much is know about its function. Preliminary data found, using newly developed techniques, has revealed oscillation of cAMP triggered by glucose that correspond with increased calcium levels.

Objective: Use the evanescent-wave microscopy technique for real time recordings of cAMP, as well as single-cell recordings of insulin release to study enzyme kinetics of glucose induced cAMP in conjunction with insulin secretion.

Results:

• In mouse derived MIN6 beta cells an increase in glucose was followed by increase of cAMP in oscillating patterns as seen using CFP/YFP florescence. Following this trend, a larger induced glucose concentration revealed a larger coupled cAMP response.
• After the analysis of cAMP oscillations in comparison to glucose induced calcium influxes in MIN6 beta cells it was seen that calcium enhances the increase in glucose induced cAMP but is not essential for this rise.
• In cells containing increased calcium, a correlation was found between cell metabolism and cAMP production where cell metabolism acted as a trigger for cAMP. Researchers confirmed this idea, by increasing ATP levels within the cell using oaubain which also showed an increase in cAMP production.
• Finally, ending studies revealed cAMP oscillations played a key role in the pulsatile secretion of  insulin. For each pulsatile release of insulin from the pancreatic beta cells, a coordinating cAMP oscillation preceded secretion.

-JI 

Adult Neurogenesis Produces Neurons with Unique GABAergic Synapses in the Olfactory Bulb.

Valley MT, Henderson LG, Inverso SA, Lledo PM.
J Neurosci. 2013 Sep 11;33(37):14660-5. PMID:    24027267

Objective:   In adult mammals, interneurons are continuously generated in the olfactory bulb, many of which later become granule cells.  It is known that the immature cells are integrated in to neural circuits and receive inputs that contribute to whether or not they will live or die, but little has been shown about the differences in this fate-deciding process between early and late stages of an organism’s life.  In this paper, it was found that regulation by the GABAB receptor mediated presynaptic regulation is absent in adult-born cells, but not in cells born during neurogenesis.

Results:

·         Recordings from postsynaptic mitral cells (MCs) during photostimulation of channelrhodopsin-expressing presynaptic granule cells (GCs) showed inhibitory post synaptic currents (IPSCs) that could be blocked by GABAA antagonists or application of TTX, suggesting that photostimulation caused GABA release from GCs on to MCs.

·         Application of the GABAB receptor agonist R/S-baclofen caused a decrease in IPSCS caused by photostimulation of early-born GCs, but not in GCs born at postnatal day 60.  They found that GABAB receptor function was not linked to the age of the cell, but rather that aged early-born cells retained receptor function while younger late-born cells did not have GABAB receptor function.

·         After lentiviral expression of markers to differentiate GCs born on p6 and p60, immunoreactivity for the GABAB1 subunit of GABAB was assayed.  P60 GCs had greater dendritic and internal GABAB1, while p6 GCs had greater axonal GABAB1.  This shows that GCs born at different times throughout an animal’s life can have different distribution of the same receptor.

 

Methods:    Mice were anesthetized and their olfactory bulbs were given bilateral injections of lentivirus containing a cassette that had channelrhdopsin2(H134R)eYFP under the control of the synapsin promoter.  After allowing time for gene expression, slices were made from the olfactory bulbs and MCs were held under voltage clamp at +10mV in order to monitor IPSCs.  In animals used for immunohistochemistry, the brain was removed and fixed with 4% paraformaldehyde.

 -DH

Cortical balance of excitation and inhibition is regulated by the rate of synaptic activity.

Taub AH, Katz Y, Lampl I.
J Neurosci. 2013 Sep 4;33(36):14359-68. PMID: 24005289

Objective:   Neurons are constantly integrating excitatory and inhibitory inputs transmitted by other cells.  These inputs increase or decrease during different brain states, and the cells themselves are able to regulate their own responses to the collective input.  How these balances shift can be counterintuitive and misunderstood.  In this paper, the authors examined the effect of light and deep anesthesia on excitatory and inhibitory inputs to cortical neurons and found that under deep anesthesia, presynaptic inhibitory cells are inhibited, which causes increases in the amplitude and duration of inhibitory neurotransmissions on the postsynaptic cell.

Results:

·         Under deep anesthesia, increased low-frequency EEG power was noted.  They also saw a decrease in EPSP and IPSP frequency.  However, they saw that the amplitudes and widths of IPSPs were larger, but those of EPSPs were not.

·         The altered characteristics could be due to presynaptic or postsynaptic changes.  The membrane characteristics of postsynaptic cells were examined and demonstrated no changes in resting potential or input resistance across levels of anesthesia.

·         These effects were not due to halothane, as rats given ketamine/halothane, propofol/halothane, propofol alone, and ketamine alone all showed the same effects.

·         Cells were examined for the recovery of spontaneous EPSPs and IPSPs after intracortical electrical stimulus trains.  They found that EPSPs recovered their amplitude and frequency faster than IPSPs, suggesting that a decrease in IPSP frequency could be responsible for the greater amplitude during anesthesia-induced inhibition.  They further investigated this observation by examining the envoked-IPSPs and found that there was an inverse correlation between stimulus frequency and IPSP amplitude, regardless of the level of anesthesia.

·         Methods:    4-8 week old rats were lightly or deeply anesthetized with halothane or halothane with propofol or ketamine and used for EEG recordings.  Whole-cell recordings were performed under current clamp with sufficient current applied to hold the cell at predesignated voltages which would enable clear observation of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs).  Cells were identified in vivo by well-established characteristics.  Electrical stimulations were performed with a tungsten electrode positioned just below the recording site.

-DH

The importance of serotonin in exercise-induced adult neurogenesis: new evidence from tph2-/- mice.

Beckman D, Santos LE.
J Neurosci. 2013 Sep 4;33(36):14283-4. PMID: 24005280

Objective:   Serotonin signaling is known to be involved in the process of adult neurogenesis.  Decreases in neurogenesis are known to occur in people with depression while treatment with monoaminergic therapy can help offset the loss.  Since exercise is also linked to mood and neurogenesis, this review paper examines some of the recent literature in order to show links between exercise and serotonin in the generation and maintenance of neurons.

·         Knockout mice deficient in the rate-limiting enzyme involved in serotonin synthesis, tryptophan hydroxylase (Tph2), develop different from control littermates and show decreases in growth and increased behavioral disorders.  When allowed free access to a running wheel for 6 days, knockout mice showed less hippocampal neurogenesis than controls, despite starting with the same total number of cells.  Since lesions in the main ascending serotonergic nucleus do result in decreased neurogenesis, this suggests a compensatory mechanism in knockout mice

·         Knockout mice also show reductions in levels of dopamine and noradrenaline, both of which have been implicated in controlling proliferation of hippocampal cells.

·         Using markers for cell proliferation and apoptosis, it has been seen that knockout mice show less hippocampal proliferation and more apoptosis than controls.

·         Knockout mice show greater microgliosis after exercising, suggesting that serotonin may be involved in suppressing inflammation.  This hypothesis is supported by other work showing that serotonin reuptake inhibitors can suppress inflammation.

-DH

Differential amino acid transmission in the locus coeruleus of Wistar Kyoto and spontaneously hypertensive rats.

Naunyn Schmiedebergs Arch Pharmacol. 2004 Nov;370(5):381-7. Epub 2004 Oct 23.

Kaehler ST, Salchner P, Singewald N, Philippu A.

Source

Department of Pharmacology and Toxicology, University of Innsbruck, Austria

Previously it was known that Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) differ in their emotional behaviour. It is also known that both groups differ in their blood pressure. In this study the authors wanted to test if there is any difference in the release rate of GABA and glutamate in the locus coeruleus. Locus coeruleus, is a nucleus in the brainstem that is known to be involved in the physiological responses to stress, it is activated by stress, and will respond by increasing norepinephrine secretion and it mediates many sympathetic effects during stress. WKY rats show normal blood pressure and enhanced anxiety related behaviour when compared to SHR rats with high blood pressure and low anxiety. When experimental hypertension was induced with noradrenaline GABA release went up in WKY rats but no changes were seen in SHR rats. Glutamate release was not affected under the above condition. Upon administration of sodium nitroprusside the blood pressure went down in both groups but the aminoacid release was not affected. Mild stress was induced by tail pinching which led to an increase in the release of glutamate and GABA in locus coeruleus of both groups. In conclusion, SHR and WKY rats differ in GABAnergic neurotransmission, in response blood pressure challenges, but not to mild stressors. A disturbed mechanism counteracting high blood pressure may be responsible for the observed lack of GABA response to blood pressure elevation in SHR and that may possibly contribute to hypertension in this strain.

-Madhan

Aminopropionic acid receptors in paraventricular nucleus mediate pressor and vasopressin responses to endothelin-1 in subfornical organ.

Exp Biol Med (Maywood). 2006 Jun;231(6):1075-80.
Rossi NF, Chen H.
Source

Departments of Medicine and Physiology, Wayne State University School of Medicine and John D. Dingell VA Medical Center, Detroit, Michigan, USA.

Previously it has been shown that endothelin (ET-1) elicits pressor response and induces secretion of vasopressin (AVP). In this article the authors hypothesize that the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) are mediated by glutamatergic receptor within the PVN. The reason the authors chose glutamatergic receptors is because they are shown to mediate ET-1-induced AVP secretion in vitro. In this study sinoaortic denervated male Long Evans rats were implanted with icv cannulae bilaterally in the SFO and PVN. ET-1 was directly injected into the SFO resulting in an increase in mean arterial pressure (MAP) and mean plasma AVP level, these changes were blocked by selective ET (A) inhibition. Pretreatment with an NMDA blocker diclozipine into PVN bilaterally showed no changes in MAP and MPV. However, when 6-cyano-7-nitroquinoxaline-2,3-dione was injected bilaterally in the PVN prevented the pressor response and also inhibited AVP secretion. In conclusion both the pressor response and AVP secretion in response to ET-1 acting at the SFO are mediated by a non-NMDA, most likely an aminopropionic acid glutamatergic receptor within the PVN.

-Madhan

Upregulation of AT1R and iNOS in the rostral ventrolateral medulla (RVLM) is essential for the sympathetic hyperactivity and hypertension in the 2K-1C Wistar rat model.

Am J Hypertens. 2010 Jul;23(7):708-15. Epub 2010 Apr 1.

de Oliveira-Sales EB, Nishi EE, Boim MA, Dolnikoff MS, Bergamaschi CT, Campos RR.

In this study, the role of iNOS and AT1R in the RVLM in the development of hypertension in the 2 kidney 1 clip rat model has been studied. After 6 weeks of renal surgery, the rats were divided into sham and hypertensive rats. iNOS and AT1R receptor expression was studied in the RVLM punches of both the groups of rats. iNOS mRNA and the protein levels of iNOS and AT1R receptor in the RVLM of rats that underwent renal surgery were higher than the sham operated rats. Also injection of losartan (AT1Rantagonist) and aminoguanidine (iNOS inhibitor) in the RVLM of 2K-1C hypertensive rats resulted in a decrease in the mean arterial pressure and renal sympathetic activity. On the other hand, no difference in any of the parameters was observed in the sham operated animals without hypertension. This study demonstrates that AT1R and iNOS are important in maintaining arterial hypertension in 2K-1C model hypertension.

- Madhan

Effect GABA A receptors in the RVLM on cardiovascular response to the activation of the Bed nucleus of the stria terminalis in female ovariectomized rats

 

 

Effect of GABA A Receptors in the Rostral Ventrolateral Medulla on Cardiovascular

 

Response to the Activation of the Bed Nucleus of the Stria Terminalis in Female

Ovariectomized Rats
 
Masoumeh Hatam, Mahin Ganjkhani

Background:Cardiovascular diseases rarely affect women before menopause, this may suggest that estrogen might be cardioprotective.. The Bed nucleus of stria terminalis (BST) that concentrat estrogen and aromatase enzyme, this enzyme converts testosterone to estrogen.

Purpose of study:
1.Does estrogen have an affect on cardiovascular function
2.They wanted to investigate whether the inhibitory affect on cardiovascular response seen in response to stimulation of the BST was being mediated in part by the RVLM.
3. Are GABAergic mechanism involved in the RVLM to help mediate the response to stimulation of the BST.

Results:They found that glutamate into the BST caused a decrease in MAP and HR. When COCl2 was injected into the RVLM there was attentuation of the MAP and HR response. Then to determine if GABA A receptors or GABA B recptors are mediating the response bicuculline was injected into the RVLM and the BST was stimulated with glu and the response was significantly smaller than pre responses without bicuculline. They repeated the same protocol with phaclophen into the RVLM and it had no affect on the response to stimulation of the BST. The only differences they saw between the OVX +E and OVC-C was that the OVX+E had lower baseline HR.

Conclusion: These data demostrate that estrogen has an effect on cardiovascular function. It also demostrates that in response to BST stimution the activity of RVLM neurons is inhibited and this inhibition is mediated by GABA A receptors. 
 
  

Exercise training causes sympathoinhibition through antioxidant effect in the rostral ventrolateral medulla of hypertensive rats

Exercise Training Causes Sympathoinhibition Through Antioxidant

Effect in the Rostral Ventrolateral Medulla of Hypertensive Rats


Takuya Kishi,Yoshitaka Hirooka,2 Masato Katsuki,1 Kiyohiro Ogawa,1 Keisuke Shinohara,Kengo Isegawa,Kenji Sunagawa1

Background: Exercise training (extr) reduces SNS activity in heart failure (hf). Exercise also enhances baroreflex sensitivy in hf. In the RVLM oxidativae stress enhances SNS activity via AT1R activiation. Other studies have shown that NO in RVLM leads to deceased SNS activity. It may be possible that an imbalance of NO and oxidative stress could cause cardiovascular diseases.

Aim: This study investigated the effects of exercise training on SNS activity and oxidative stress in the RVLM of hypertensive rats.

Methods: They measured MAP, HR, and urinary NE excretion as a measurement of SNS activity, bbarosensitivity, and oxidative stress in the RVLM of hypertensive and norm rats with exercisse training. They used tempol in the RVLM to inhibit oxidative stress. Also they injected ang II in the RVLM of hypertensive and Norm rats with exercise training.

results/findings: first they found that extr caused smpathoinhibition and improved the impaired baroreflex sensitivity in the SHRSP. They also found that extr reduced oxidative stress in RVLM of SHRSP. finally they demostrated that the depressor response caused by tempol and angII pressor responses in RVLM caused smaller responses with extr compared to control.

Conclusion: Extr causes sympathoinhibition and improves impaired baroreflex sensitivity via antioxidant in the RVLM through blocked AT1R in RVLM.

Inhibition of Neurogulin-1/ErbB signaling in the RVLM leads to hypertension through reduced nitric oxide synthesis

Inhibition of Neuregulin-1/ErbB Signaling in the Rostral Ventrolateral Medulla Leads to Hypertension through Reduced Nitric Oxide Synthesis

Ryuichi Matsukawa, Yoshitaka Hirooka, Koji Ito, and Kenji Sunagawa
Background :Neuregulin-1 (NRG-1) binds to ErbB receptors. NRG-1/ ErbB signaling in the RVLM may have antihypertensive affects . It has been shown that ErbB signaling in RVLM is impaired in spontaneously hypertensive rats due to reduced ErbB2 expression.

Aim: The purpose of this study is to determine whether ErbB2 inhibition in the RVLM contributes to increasin blodd pressure via modulation of NO and GABA.

Methods:
They did intracisternal infusion of ErbB2 antagonist and the MAP and HR were monitored using telemetry. They also used siRNA in order to knock down ErbB2 expression in RVLM. Final they investigated protein expression of ErbB2, pErbB2 nNos, and eNOS in RVLM using western blot.

Results/ findings:
In response to the intracisternal infusion of the antagonist they found tha MAP, HR uNE were increased compared to the control. They also found that pErbB2, nNOS and eNOSwere lower in the treatment group compared to the control.In response to NOS blockade there was an increase in uNE on day 14 compared to before treatment. As for the ErbB2 siRNA, it lead to increased MAP and HR after 1 day of treatment . nNos and eNOS both were lower in ErbB2 siRNA group compared to control.

Conclusion:Study demostrates that attentuation of ErbB2 activity inRVLM causes hypertension by reducing NOS expression.

Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat.

AUTHORS Challis C, Boulden J, Veerakumar A, Espallergues J, Vassoler FM, Pierce RC, Beck SG, Berton O.
J Neurosci. 2013 Aug 28;33(35):13978-88. PMID: 23986235

 

Objective:   The ascending serotonin (5-HT) pathway originates primarily in the dorsal raphe nucleus (DRN) and is known to play a role in aggression, avoidance, dominance, and a variety of other behaviors.  Though it is known that the DRN has a strong involvement in behavior, surprisingly little is known about the regulation of the heterogeneous cells in this area.  While much of the existing literature about this area has been about the serotonergic cells of the DRN, this paper examines the role of DRN GABAergic neurons in the negative regulation of the 5-ht neurons of the DRN.

Methods:    Mice were bred to express tdTomato in either GABAergic or serotonergic cells by mating floxed-stop reporter mice with mice expressing Cre under the control cell-type-specific promoters.  Mice expressing Cre in GABAergic neurons were injected with AAV that delivered a Cre-inducible archeorhodopsin in order to inhibit the neurons with photostimulation.  Mice were fitted with fiber optic cannula in to the DRN to allow for photoactivation of the inhibitory light-gated anion channel, archeorhodopsin.  After 6 weeks, mice were challenged with repeated social defeat, open field test, and elevated plus-maze.  In some mice, slices of brain containing the DRN were taken for whole-cell patch clamp recording.  Mice were transcardially perfused with 4% paraformaldehyde and the brains were processed for immunohistochemistry.  

Results:

·         Mice experiencing repeated social defeat showed an increase in cFos expression in the ventrolateral DRN, where 5-HT neurons are sparse.  This area corresponded to regions receiving input from the prefrontal cortex, which is involved in social cognition.  There was increased cFos in cells also expressing a marker for GABA synthesis.

·         GABAergic neurons were located by tdTomato expression and used for whole-cell recording.  They were found to have properties different from 5-HT cells, in terms of increased spontaneous activity, shorter action potential duration, and higher membrane resistance.  GABAergic neurons from mice susceptible to social defeat showed more excitatory post synaptic currents as well as more action potentials per current injection than controls or mice resistant to defeat.  5-HT neurons of mice susceptible to social defeat showed decreased excitability and more inhibitory post synaptic currents.

·         Stimulation of slices with 543nm light activated archeorhodopsin, resulting in silencing of spontaneous action potentials in GABA neurons.  Photoactivation of archeorhodopsin caused a significant decrease in the frequency of miniature inhibitory postsynaptic potentials in 5-HT neurons, demonstrating a local monosynaptic inhibitory connection between GABA producing neurons and serotonergic neurons within the dorsal raphe nucleus (for the first time in the literature).  When the GABAergic cells were silenced during the social defeat training protocol, mice showed significantly less defeat (time spent interacting) during the testing phase than mice that did not have photo-silencing of GABAergic neurons.  However, when GABAergic neurons were silenced during the testing phase (after the development of social defeat), photostimulation did not increase interaction time.  This indicates that GABAergic neurons of the DRN are involved in encoding of the defeat behavior, but not during the execution of pre-established defeat.

·         In contrast with suggestions in previous literature, optogenetic inhibition of the encoding of social defeat did not result in a decrease in more generalized anxiety as shown by the open field and eleveated plus maze tests.

 

-DH