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[0] Narayanan NS, Kimchi EY, Laubach M, Redundancy and synergy of neuronal ensembles in motor cortex.J Neurosci 25:17, 4207-16 (2005 Apr 27)

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ref: -0 tags: Courtine e-dura PDMS silicone gold platinum composite stretch locomotion restoration rats date: 12-22-2017 01:59 gmt revision:0 [head]

PMID-25574019 Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

  • Fabrication:
    • 120um total PDMS thickness, made through soft lithography, covalent (O2 plasma) bonding between layers
    • 35nm of Au (thin!) deposited through a stencil mask.
    • 300um Pt-PDMS composite for electrode sites, deposited via screenprinting
  • 100 x 200um cross section drug delivery channel.
  • Compared vs. stiff 25um thick PI film electrode.
    • stiff implants showed motor impairments 1-2 weeks after implantation.
  • Showed remarkable recovery of supported locomotion with stimulation and drug infusion (to be followed by monkeys).

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ref: -0 tags: neural coding rats binary permutation retrosplenial basolateral amygdala tetrode date: 12-19-2016 07:39 gmt revision:1 [0] [head]

PMID-27895562 Brain Computation Is Organized via Power-of-Two-Based Permutation Logic.

  • Nice and interesting data, sort of kitchen sink of experiments but ...
  • At first blush it seems they have re-discovered Haar wavelets / the utility of binary decompositions.
  • Figures 9 and 10, however, suggest a discriminable difference in representation in layers 2/3 and 5/6, supporting their binary hypothesis.
    • The former targeted the mouse's large retrosplenial cortex; the latter, the hamster's prelimbic cortex.

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ref: Musallam-2007.02 tags: Musallam MEA floating rats electrodes date: 01-28-2013 00:42 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-17067683[0] A floating metal microelectrode array for chronic implantation

  • Cite Gualtierotti and Bailey (1968) for a neutral-boyancy electrode w/ rigid shaft.
  • Alumina ceramic base, laser drilled.
  • insulated with silane follwed by parylene-C, 3um.
  • Tips exposed by eximer laser. (Schmidt et al, 1995)
  • Electrophysiology, but not histology.
  • Earlier conference proceedings: PMID-17946982[1] Active floating micro electrode arrays (AFMA).

____References____

[0] Musallam S, Bak MJ, Troyk PR, Andersen RA, A floating metal microelectrode array for chronic implantation.J Neurosci Methods 160:1, 122-7 (2007 Feb 15)
[1] Kim T, Troyk PR, Bak M, Active floating micro electrode arrays (AFMA).Conf Proc IEEE Eng Med Biol Soc 1no Issue 2807-10 (2006)

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ref: Sanders-2000.1 tags: polymer fiber immune reaction biocompatibility rats polycaprolactone recording electrodes histology MEA date: 01-28-2013 00:01 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-10906696[0] Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

  • Fibers smaller than 6μm show reduced immune response.
    • Fibers implanted in the subcutaneous dorsum (below the skin in the back of rats).
    • Polypropylene. (like rope).
    • Wish the result extended to small beads & small electrodes. 7μm is tiny, but possible with insulated Au wires.
      • Beads: try PMID-1913150 -- shows that the 600um - 50um beads ('microspheres') are well tolerated.
      • Also {750}.
  • Macrophage density in tissue with fiber diameters 2.1-5.9um comparable to that of unoperated contralateral control.

"

fiber diametercapsule thickness
2.1-5.90.6
6.5-10.611.7
11.1-15.820.3
16.7-26.725.5

____References____

[0] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

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ref: Stice-2007.06 tags: electrodes recording small rats S1 PGA histology GFAP date: 01-24-2013 21:07 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-17409479[0] Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.

  • Implanted 12 um and 25 um polymide coated stainless steel
    • Wires coated with poly-glycolic acid (PGA) to facilitate implantation.
  • Only looked to 4 weeks.
  • 12 um implants significantly less GFAP (astrocyte) reactivity at 4 weeks, no difference at 2 weeks (figure 9 & 10).
    • B = bare, P = PGA coated.
  • Can use to bolster the idea that smaller implants are less irritating.

____References____

[0] Stice P, Gilletti A, Panitch A, Muthuswamy J, Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.J Neural Eng 4:2, 42-53 (2007 Jun)

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ref: Freire-2011.01 tags: Nicolelis BMI electrodes immune respones immunohistochemistry chronic arrays rats 2011 MEA histology date: 06-29-2012 01:20 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22096594[0] Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.

  • Says what might be expected: tungsten microelectrode arrays work, though the quality gradually declines over 6 months.
  • Histological markers correlated well with recording performance.
  • Shows persistent glial activation around electrode sites + cell body hypertropy.
    • Suggest that loss in recording quality may be due to glial encapsulation.
  • References
    • Szarowski et al 2003 {1028}
    • Ward et al 2009
  • Histology:
    • NADPH-d: nicotinamide adenine dinucleotide phosphate-diaphorase, via beta-NADP
    • CO: cytochrome oxidase, via diamnibenzidine DAB, cytochrome c and catalase.
      • both good for staining cortical layers; applied in a standard buffered solution and monitored to prevent overstaining.
  • Immunohistochemistry:
    • Activated microglia with ED-1 antibody.
    • Astrocytes labeled with glial fibrillary acid protein.
    • IEG with an antibody against EGR-1, 'a well-known marker of calcium dependent neuronal activity'
    • Neurofilament revealed using a monoclonal NF-M antibody.
    • Caspace-3 with the associated antibody
    • Details the steps for immunostaining -- wash, blocknig buffer, addition of the antibody in diluted blocking solution (skim milk) overnight, wash again, incubate in biotinylated secondary antibody, wash again, incubate in avidin-biotin-peroxidase solution.
    • Flourescent immunohistochemistry had biotynlation replaced with alexa Fluor 488-conjugated horse anti-mouse and Alexa Fluor 594-conjugated goat anti-rabbit overnight.

____References____

[0] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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ref: -0 tags: bilateral STN lesion rats perseverence nose poke impulsivity DBS basal ganglia date: 02-29-2012 17:44 gmt revision:1 [0] [head]

PMID-9421169 Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats.

  • Excitotoxic lesion of STN alleviate motor impairment found in PD dopamine depletion model.
  • What about normal rats?
  • investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five-choice test of divided and sustained visual attention, modelled on the human continuous performance task.
  • This task required the animals to detect a brief visual stimulus presented in one of five possible locations and respond by a nose-poke in this illuminated hole within a fixed delay, for food reinforcement
  • STN lesion:
    • decreased discriminatory activity
    • increase premature responses & preservative panel pushes and nose-poke responses.
  • Subsequent D1/D2 anatagonist administration reduced premature responses but not preservative nose-pokes.
  • Consistent with action selection and inhibition.
  • Suggest that these cognitive-type effects should be examined in humand that have STN DBS.

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ref: Mallet-2008.04 tags: DBS oscillations STN beta 6-OHDA rats ECoG acute date: 02-29-2012 01:11 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18448656[0] Disrupted dopamine transmission and the emergence of exaggerated beta oscillations in subthalamic nucleus and cerebral cortex.

  • STN has pronounced beta band oscillations in PD patients.
  • 6-OHDA rodent model (here) shows the same, depending on state.
    • Synchronization in both local cellular assemblies and broadly across the STN + ECoG.
    • ECoG looks causal in their studies.
    • Frequencies > 15 Hz, not lower (theta), as in other studies.
  • Excessively synchronized beta oscillations reduce the information coding capacity of STN neuronal ensembles, which may contribute to parkinsonian motor impairment.
  • Acute disruption of dopamine transmission in control animals with antagonists of D(1)/D(2) receptors did not exaggerate STN or cortical beta oscillations.
    • This despite the potent agonist induced catalepsy in the rats!
    • Must be neural plasticity & structural.
    • Takes > 4 days.
    • Actual striatal DA levels decrease within 1 h of midbrain 6-OHDA
  • Under normal conditions, beta synchronization may be useful for sensory-motor processing (Uhlhaas and Singer 2006).
  • Synchronized activity is preferentially transmitted due to temporal summation.

____References____

[0] Mallet N, Pogosyan A, Sharott A, Csicsvari J, Bolam JP, Brown P, Magill PJ, Disrupted dopamine transmission and the emergence of exaggerated beta oscillations in subthalamic nucleus and cerebral cortex.J Neurosci 28:18, 4795-806 (2008 Apr 30)

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ref: Boulet-2006.1 tags: hemiballismus PD parkinsons STN subtalamic DBS dyskinesia rats 2006 glutamate date: 02-22-2012 18:58 gmt revision:1 [0] [head]

PMID-17050715 Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked to an Increase in Glutamate Levels in the Substantia Nigra Pars Reticulata

  • STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr.
    • Well, that just makes sense. STN is excitatory, GPi is an output structure of the BG, and stimulation should activate the area.

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ref: Teagarden-2007.03 tags: STN striatum operant conditioning behavior rats 2006 DBS date: 02-15-2012 03:36 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17182916[0] Subthalamic and Striatal Neurons Concurrently Process Motor, Limbic, and Associative Information in Rats Performing an Operant Task

  • STN encodes behavioral events (reinforcement, nose poke, correct / incorrect trials). So does the striatum.
  • This study is rather nonspecific, but it makes sense that a conserved and well connected region is active during learning & general behavior.
    • That is, while the subthalamic nucleus is considered an output relay of the basal ganglia, more likely it operates in parallel to facilitate forms of learning; as such, responses are shown to rewards, cues, etc.

____References____

[0] Teagarden MA, Rebec GV, Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task.J Neurophysiol 97:3, 2042-58 (2007 Mar)

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ref: Wiener-2008.08 tags: STN operant conditioning timing rats lesion DBS impulsivity date: 01-26-2012 17:29 gmt revision:3 [2] [1] [0] [head]

PMID-18562098[0] Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus.

  • Synopsis: Animals whose STNs were lesioned were able to maintain temporal control and response on a peak interval timing task, but they were unable to inhibit operant responses late into the trial. This suggests that STN may be used in impulse control / behavioral inhibition.

____References____

[0] Wiener M, Magaro CM, Matell MS, Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus.Neurosci Lett 440:2, 176-80 (2008 Aug 1)

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ref: Florio-2001.11 tags: STN PPN lesions preparatory rats DBS date: 01-26-2012 17:22 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11704255[0] Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat.

  • the title says it all ;)
  • they describe hemiballismus as "stereotyped repetitive involuntary movements of the cotralateral limbs" (might have to see this to understand it)
  • what the rat had to do:
    1. press lever 1 upon trigger 1 stimuli
    2. wait 3-4 seconds for the trigger 2 stimuli
    3. then press lever 2, upon which a pellet of food was given to the rat.
  • lesions of the STN in the rat do not induce hyperkinetic movements in overt behaviors, but cause anticipatory motor responses in delayed-reaction tasks, like a nose-poke.
    • see figure 7 for the bar-graph of this.
    • rats tended to release the lever before the reward or CS for reward was triggered
    • still - this might be a cognitive problem, not a lack of anticipation.
  • the PPN has remarkable reciprocating connections with the STN, and other basal ganglia nuclei
    • PPN lesion increases reaction time during conditioned movements, making the animals bradykinetic or akinetic
      • "the animals bearing the combined lesion were severely impaired in conditioned responding to salient stimuli involved in the paradigm and showed side-specific lengthening of reaction and movement times without global motor impairments."
      • has anybody looked at activity in the PPN of parkinsonian monkeys? hum.
    • compare to [1] - PPN lesions can restore normal activity in SNr & STN. but, if you don't have the STN to restore, then PPN doesn't matter.

____References____

[0] Florio T, Capozzo A, Cellini R, Pizzuti G, Staderini EM, Scarnati E, Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat.Behav Brain Res 126:1-2, 93-103 (2001 Nov 29)
[1] Breit S, Lessmann L, Unterbrink D, Popa RC, Gasser T, Schulz JB, Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model.Eur J Neurosci 24:8, 2275-82 (2006 Oct)

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ref: Parikh-2009.04 tags: BMI rats cortex layer depth date: 01-10-2012 01:09 gmt revision:2 [1] [0] [head]

PMID-19255460[0] Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses.

  • Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05).
  • DUH. Have we forgotten all anatomy?

____References____

[0] Parikh H, Marzullo TC, Kipke DR, Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses.J Neural Eng 6:2, 026004 (2009 Apr)

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ref: Olds-1967.01 tags: Olds 1967 limbic system operant conditioning recording rats electrophysiology BMI date: 01-06-2012 03:59 gmt revision:2 [1] [0] [head]

PMID-6077726[0] The limbic system and behavioral reinforcement

  • Can't seem to find Olds 1965, as was a conference proceeding .. this will have to do, despite the lack of figures. images/966_1.pdf
  • First reference I can find of chronic (several weeks) (4-9 microelectrodes, single) recording from the rat.
  • Basically modern methods: commutator + solid state preamplifiers mounted to a counterbalanced slack-relieving arm.
    • If unit responses were observed in recordings from a given probe a week after surgery they were usually recordable indefinitely. 44 years later ...
  • Used a primitive but effective analog spike discriminator based on:
    • minimum amplitude
    • maximum amplitude
    • minimum fall time
    • maximum fall time.
  • Also had a head movement artifact detector, which blanked the recordings (stopped the paper roll) for 2 sec.
  • Reinforced on 'bursting', threshold sufficiently high that it only occurred once every 5-15 minutes.
  • Food reinforcement or 1/4 second train of brain stimulation (30ua, 60Hz, sine, in hypothalamus).
  • Reinforcement was conditioned on an 'acquisition' signal, which is visual (?) Bursting is rewarded for 2 minutes, ignored for 8 minutes.
  • Also recorded control neurons.
  • (they were looking at these things as though anew!) "The most striking aspect of the records so formed [on sheets of paper] was that all discriminators at one time or another exhibited rate changes that had the appearance of waves with a period of 10 to 20 minutes. Waves between units in the same animal were to some degree synchronized." Then describes a ramp ..
  • Longer term variations: FR would vary by a factor of 2-5 over a period of several hours.
    • This would make negatively correlated neurons (on a short time scale) appear positively correlated over long time scales (have to fix this in the BMI!)
  • As this was a conditional reinforcement task, they unexpectedly found that the acquisition periods were systematically different than extinction periods
    • More like pavlovian conditioning, esp in the hippocampus, where a conditioned response was also reflected on a control neuron.
    • Even when the light was lit throughout the acquisition period was replaced by a bell at the beginning of the acq. period, there was still a sustained change in FR.
      • Then during the extinction period: it appeared from the record of responses that a definite operant behavior was tried several times and then stopped altogether."
  • In the pontine nucleus (relay from M1 to cerebellum, v. roughly), judging from the control responses, all were conditioned.
    • Pontine responses seem to correspond with movement of the eyes or head that did not set off the movement detector/blanker.
  • Saw brief and very fast bursts during the extinction periods of the kind that Evarts found to characterize pyramical neurons during sleep.
  • When units shifted from food reward to ICS reward, units became undiffarentiated, and within a day they would be reconditioned.
  • Also tried paralyzing the animal to see if it could still generate operant responses; the animal died, results inconclusive.
  • Flood lights made it hard for the rats to produce the operant behavior.

____References____

[0] Olds J, The limbic system and behavioral reinforcement.Prog Brain Res 27no Issue 144-64 (1967)

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ref: Nicolelis-1997 tags: nicolelis microwire array electrophysiology rats date: 01-05-2012 03:35 gmt revision:2 [1] [0] [head]

PMID-9136763[0] Reconstructing the engram: simultaneous, multisite, many single neuron recordings.

  • descibes Miguel's microwire arrays.
  • 100 units from 48 microwires in rats.
  • 2.3 units / microwire.
  • stable for weeks -- c.f. 2011. [1]

____References____

[0] Nicolelis MA, Ghazanfar AA, Faggin BM, Votaw S, Oliveira LM, Reconstructing the engram: simultaneous, multisite, many single neuron recordings.Neuron 18:4, 529-37 (1997 Apr)
[1] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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ref: Nicolelis-1993 tags: neurons somatosensory nicolelis rats thalamus date: 01-03-2012 23:30 gmt revision:2 [1] [0] [head]

from the Scientific American:

  • blocking (single?) neuron activity in S1 cortex affects the responses of VPM neurons in the thalamus - indicating that descending feedback signals in the cortex to the VPM could have a major role in modulating the ascending information.
  • if you implant a cuff electrode aroung the trigeminal nerve, the evoked responses in S1 and VPM are dependent on the behavioral state of the animal (of course!). this effect is so pronounced that, when the rats were not 'paying attention', only the first stimulus of a series evoked a response; when the rat was whisking, stimulation was faithfully reported.

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ref: Olson-2005 tags: Arizona rats BMI motor control training SVM single-unit left right closed-loop learning Olson Arizona date: 01-03-2012 23:06 gmt revision:1 [0] [head]

bibtex:Olson-2005 Evidence of a mechanism of neural adaptation in the closed loop control of directions

  • from abstract:
    • Trained rats to press left/right paddles to center a LED. e.g. paddles were arrow keys, LED was the cursor, which had to be centered. Smart rats.
      • Experiment & data from Olson 2005
    • Then trained a SVM to discriminate left/right from 2-10 motor units.
    • Once closed-loop BMI was established, monitored changes in the firing properties of the recorded neurons, specifically wrt the continually(?) re-adapted decoding SVM.
    • "but expect that the patients who use the devices will adapt to the devices using single neuron modulation changes. " --v. interesting!
  • First page of article has an excellent review back to Fetz and Schmidt. e.g. {303}
  • Excellent review of history altogether.
    • Notable is their interpretation of Sanchez 2004 {259}, who showed that most of the significant modulations are from a small group of neurons, not the large (up to 320 electrodes) populations that were actually recorded. Carmena 2003 showed that the population as a whole tended to group tuning, although this was imperfectly controlled.
  • Also reviewed: Zacksenhouse 2007 {901}
  • SVM is particularly interesting as a decoding algorithm as it weights the input vectors in projecting onto a decision boundary; these weights are experimentally informative.
  • Figure 7: The brain seems to modulate individual firing rate changes to move away from the decision boundary, or at least to minimize overlap.
  • For non-overt movements, the distance from decision function was greater than for overt movements.
  • Rho ( ρ ) is the Mann-Whitney test statistic, which non-parametrically estimates the difference between two distributions.
  • δf(X t) is the gradient wrt the p input dimensions o9f the NAV, as defined with their gaussian kernel SVM.
  • They show (i guess) that changes in ρ are correlated with the gradient -- e.g. the brain focuses on neurons that increase fidelity of control?
    • But how does the brain figure this out??
  • Not sure if i fully understand their argument / support.
  • Conclusion comes early in the paper
    • figure 5 weakly supports the single-neuron modulation result.

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ref: Eschenko-2006.12 tags: sleep spindle learning rats date: 03-20-2009 00:40 gmt revision:1 [0] [head]

PMID-17167082[0] Elevated sleep spindle density after learning or after retrieval in rats.

  • sleep spindles = 12–15 Hz oscillations superimposed on slow waves (<1 Hz)
    • they say these 'promote' but infact they may just be effects of some lower-level synchronization / ensemble depolarization.
  • used an odor-response-reward task.
  • spindles reliably appear 1 hour after sleep begins.
  • hippocampal ripples are temporally related to cortical spindles and both are grouped by slow oscillations.
  • showed that pure exploration of novel environments (without the odorant pairing) does not change sleep spindle occurence frequency.

____References____

[0] Eschenko O, Mölle M, Born J, Sara SJ, Elevated sleep spindle density after learning or after retrieval in rats.J Neurosci 26:50, 12914-20 (2006 Dec 13)

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ref: Narayanan-2005.04 tags: Laubach M1 motor rats statistics BMI prediction methods date: 09-07-2008 19:51 gmt revision:4 [3] [2] [1] [0] [head]

PMID-15858046[] Redundancy and Synergy of Neuronal Ensembles in Motor Cortex

  • timing task.
  • rats.
  • 50um teflon microwires in motor cortex
  • ohno : neurons that were the best predictors of task performance were not necessarily the neurons that contributed the most predictive information to an ensemble of neurons.
  • most all contribute redundant predictive information to the ensemble.
    • this redundancy kept the predictions high, even if neurons were dropped.
  • small groups of neurons were more synergistic
  • large groups were more redundant.
  • used wavelet based discriminant pursuit.
    • validated with draws from a random data set.
  • used R and Weka
  • data looks hella noisy ?

____References____

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ref: Shapovalova-2006.1 tags: dopamine learning neocortex rats russians D2 date: 03-12-2007 01:58 gmt revision:0 [head]

PMID-17216714 Motor and cognitive functions of the neostriatum during bilateral blocking of its dopamine receptors

  • systemic application of D1 selective blockers reduced learning in rats
    • probably this effect is not neostriatal:
  • local application of the same blocker on the cortex did not markedly affect learning, though it did effect initiation errors
  • D2 antagonist (raclopride) locally applied to the striatum blocked learning.

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ref: notes-0 tags: leptin depression weight fat rats date: 0-0-2007 0:0 revision:0 [head]

  1. lepin is released by fat cells & gives the brain a reading of fat stores.
  2. obese people have high leptin levels, but their appetite still seems high; injecting obese people with leptin seldom causes them to loose weight.
  3. leptin injections encourage stressed or depressed rats to drink coke, i mean sugary liquid.
  4. leptin levels and appetite are low p>0.5 in depressed people.

items 2-4 are not in accord with the stated purpose of leptin (1).

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ref: Stapleton-2006.04 tags: Stapleton Lavine poisson prediction gustatory discrimination statistical_model rats bayes BUGS date: 0-0-2006 0:0 revision:0 [head]

PMID-16611830

http://www.jneurosci.org/cgi/content/full/26/15/4126