Non classical Flashcards
(20 cards)
• Stuart et al (1997)
Triple recordings of AIS, soma and dendrites of a neocortical pyramidal neurons. Current injections in soma → AP initiated in AIS and could backpropagate into the dendritic tree, it gets smaller as it propagates and supported by VGNCs (TTX)
• Stuart et al (1994):
Simultaneous recording in the soma and dendrites of cerebellar Purkinje cells in rats brain slices and found APs in soma quickly degraded along dendrites and this was comparable to when applied TTX, showing that Na+ APs in cerebellar PCs are initiated in axon and passively spread through the dendritic tree
• Bjorklund and Lindvall (1975):
Using histofluorescence with glyoxylic acid in the rat brain slices showed through microscopy that SN DA neurons contained DA in the dendrites as well as the axons
o Labels CA, so assuming it is DA
• Patel et al (2009):.
Using fast scan voltammetry with guinea pig SNc neurons found that SERCA inhibition by CPA decreased extracellular DA, indicating a role of intracellular ER Ca2+ stores in somatodendritic DA release. With a mixture of pharmacological application found mGluR1-linked IP3R and RyR dependant ER Ca2+ stores facilitate somatodendritic DA release in the SNc.
• Timmerman and Abercrombie (1996):
In rats, unilateral infusion of amphetamine into SNr produced shortlasting behavioural activation that was blocked by co-infusion of the D1 DA receptor antagonist. Multiunit recordings of SNr neurons showed that AMPH induced decrease in SNR activity, coinfusion of AMPH with D1 antagonist blocked AMPH induced decrease in SNR activity therefore dendritically released DA can inhibit the activity of SNr neurons via local stimulation of D1 receptors.
• Maejima et al (2001):
): found that postsynaptic mGluR1 in PCs causes presynaptic inhibition mediated by cannabinoid receptor CB1 on excitatory CFs to reduce Glu release, suggests that mGluR1 dependant mechanisms work in synergistic manner with depolarised induced suppression to effiently modulate excitatory synaptic transmission in PC. Activation of mGLluRs in cerebellar perking cells reduced neurotransmitter release from excitatory climbing fibres and this effect was occluded by cannabinoid agonists and abolished by antagonists. The inactivation was abolished by mGluRKO
o Don’t directly show that endocannabinoids are released from the PCs,
• Katz and Miledi (1968):
the residual calcium hypothesis: where by residue of active calcium which enters the terminal axon membrane during nerve impulses is responsible for short term facilitation. Tested on NMJs by varying the local calcium concentration found that by raising the calcium of first impulse caused larger facilitation of the second
• Rice and Cragg (2004):
used fast can voltammetry using guinea pig brain slices of dorsal striatum and NAc and showed that nicotine enhances during phasic but not tonic release thus increases the contrast, by nAChR desensitisation, so seems that β2-nAChRs gate the dynamic probability of DA release. Nicotine may therefore facilitate reward-related DA signals, including responses to other primary reinforcers.
• Threlfell et al (2012):
electrophyiological recordings with ChR2 expressing cholinergic interneurons with carbon fibre microelectrodes to detect DA in striatal slices and found that optogenetic activation was sufficient to drive DA release, which dependent on nicotine antagonists, indicating that synchronised activity in cholinergic interneurons directly generates striatal DA signals whose functions will extend beyond by DA neuron activity.
• Nirenberg et al (1997)
used high resolution electron microscope immunocytochemistry in NAc and found that most DAT immunogold labelling located on extrasynaptic plasma membranes
• Yung et al (2005).
immunocytochemistry for D1 and D2 receptors in rat basal ganglia with light and electron microscopy found that a high proportion of receptors were located at extrasynaptic sites.
• Okubo et al (2010):
2 photon imaging to image glu (using EOS) in cultured hippocampal slices found that synaptic activity generates extra-synapti glu dynamics in the vicinity of active synaptses and these had magnitudes and dynamics sufficient to activate extra-synaptic glutamate receptors in brain slices. → observed cross talk between synapses. Providing evidence that glu dynamics are sufficient to activate NMDAR and mGluRs that are located on the extrasynaptic membrane to mediate volume transmission. → summate both temporally and spatially
• Tecuapetla et al (2010):
): first time deomstration that co-transmission of Glu from VTA DA neurons. Used ChR2 in VTA DA neurons in striatum in situ and used whole cell rordings in the NAc. Found post synaptic glu responses (DNQX blocked response) during evoked firing of DAergic axons that reproduce the reward-related phasic population activity of the mesolimbic projection, indicate that maybe Glu involved in reward signlaling. Blockade of D1/2 receptors had no effect nor DA depletion suggesting the effect was monosynaptic
• Tristch et al (2012):
ChR2 in nigrostriatal DA neurons and found that they corelease GABA straight onto principal neuron, in both direct and indirect MSNs, found mediated by GABAARs (antagonist no longer there) not dependant on D1/2 receptors and very fast so likely monosynaptic. Further went on to show that KO of vGAT had no effect but instead VMAT2 (used inhibitors) mediated the effect and so package DA and Glu in same vesical.
• Zhang et al (2015)
Looking at immunogold detection of VGluT2 and VMAT2 using electron microscopy and found that they were contained in distinct sites in the mesoaccumbens fibres (VTA, NAc), suggesting that there is a complex type of signalling 9in which DA and Glu are release from the same axons but not normally released at the same site or from the same synaptic vesicles
• Slim et al (2019):
Post synaptic recordings of VTA DA neurons and propose the different properties that reflect storage in different synaptic vesicles. E.g. that DA release depends on adaptor protein AP3. There vesicles different in release probability, coupling to presynaptic Ca2+ channels and frequency dependence and therefore mediates transmission of distinct signals
• Kim et al (2015):
Found that GABA is synthesised in DA neurons by aldehyde dehydrogenase 1a1 (non-canonical GABA synthesis pathway), oinhibition diminished the IPSP in MSNs but not EPSP (was not selective for DA neurons the inhibitor) KD reduced the IPSP and global KO significantly attenuated the GABA corelease but not Glu from DA neurons in the striatum. Not completely abolished so suggests that other mechanisms potentially
o None of the tests are specific to DA neurons
• Shabel et al (2014):
found that EP-LHb corelease GABA and Glu→ turned to mice and treated with citalopram and saline and found that the ratio of GABAAR and AMPAR mediated light evoked synaptic responses was higher in citalopram compared to saline treated group. Mood disorders are associated with increased activity of LHb and found that in congenital learned helplessness mice that treatment with citalopram enhanced GABA at EP-LHb synapses whereas without citalopram showed evidence in reduced GABA. Indicate that co-release of GABA and glutamate as a regulator of LHb output and potential determinant of impact of negatively valenced events on mood and behaviour.
• Di Pietro and Seamans (2011)
in vitro patch clamp recordings to measure the effects of DA and/or 5HT on pyramidal cells in layer 5 of rad mPFC and found that either 5HT or DA applied alone evoked excitability, DA and 5HT primed either larger increase in excitability than when either was alone or significant decrease showing that combined effects of DA and 5HT can be different to alone → synergistically modulate networks
Olah et al (2009)
Stimulating neurogliaform cells in the layer 2/3 cells in S1 of rats and Showed that neurogliaform cells release enough GABA for volume transmission within the axonal cloud enough not to require synapses to produce inhibitory responses and show that GABAAδ receptors are localised to neurogliaform cells preferentially among cortical interneuron and reach these receptors that are responsible for tonic inhibition. So show output of neurosteroid sensitive neuroglia cells represent the form of the lack of spatial specificity in GABA-mediated systems, leading to long lasting network hyperpolarisation combined with widespread suppression of communication in a local circuit
