Associating your work place with coffee and home with relaxation.
The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm.
Goal: To find out how different spinal cord motor neurons (MN) become specialized during development.
Results: The rostrocaudal identity of neural cells is plastic at the time of neural tube closure and is sensitive to position signals from the paraxial mesdoerm.
The method they used was by in vivo grafting either the neural tube or flanking mesoderm between the thoracic (T) and brachial (B) levels.
Organism: chick and quail. (I’ve never liked studies of other animals because they aren’t us, we have a different body and come from a different evolutionary lineage.)
Chick embryo has four major columnar MN subtypes
MNs in the medial median motor column (MMC) project axons to axial muscles.
MNs in the lateral MMC project axons to body wall muscles.
MNs in the medial lateral motor column (LMC) project axons to ventrally derived limb muscles.
MNs in the lateral LMC project axons to dorsally drived limb muscles.
Expression of Hox and LIM-HD proteins define the rostrocaudal identity of neural tube cells and the columnar subtype of spinal MNs.
Our results suggest that the generation of MN subtypes in the spinal cord involves the integration of rostrocaudal and dorsoventral patterning signals that derive from distinct paraxial and axial mesodermal cells groups.
Changes in MN columnar identity after rostrocaudal displacement of the neural tube
Examine whether the columnar identity of MNs can be respecified at a similar developmental stage by grafting segments of quail B/T neural tube into chick embryos.
T and B levels were exchanged and reversed direction.
Findings suggest that grafted neural cells have been diverted from their normal fates and that their neuronal progeny acquire the molecular properties of the new location.
Critical period of neural tube plasticity
Critical period: the period where neurons can change to a new fate.
These results suggest that by these stages, cells from B and T levels of the neural tube have been exposed to signals that specify their rostrocaudal identity and thus are no longer able to respond to host signals with a change in the columnar identity of MNs.
Plastic only within a period of approx. 12 hours.
What is somite number?
Paper provides evidence that the paraxial mesoderm has a critical role in imposing a rostrocaudal identity on cells at causal levels of the neural tube.
At spinal cord levels, the paraxial mesoderm is able to respecify cell fates in both a rostral and a caudal direction.
Signals from the paraxial mesoderm are sufficient to change the columnar identity of motor neurons.
The paraxial mesoderm is the tissue that surrounds the neural tube.
It’s unclear when signaling from the paraxial mesoderm is initiated.
Conclusion: The paper finds evidence for the role of the paraxial mesoderm in intiating the diversification of MN subtypes, but the source of the signals involved remains unknown.
E.g. It remains unclear how distinctions between MNs of the MMC and LMC, and the medial and lateral subdivisions, are defined.
Week 2
Directed Differentiation of Embryonic Stem Cells into Motor Neurons
The paper shows that developmentally relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells and into motor neurons.
They examined whether the signaling factors that operate along the rostrocaudal and dorsoventral axes of the neural tube to specify MN fate in vivo can be harnessed in vitro to direction the differentiation of mouse ES cells into functional MNs.
Steps in MN specification
Primitive ectoderm
Rostral neural
Caudal neural
Motor neurons
Growing mouse ES cells in culture for two days to form embryoid bodies (EBs).
Fig 1 shows that adding retinoic acid (RA) changes EBs to contain markers that they’re neurons.
Since exposure of ES cells to RA promotes neural differentiation and the expression of spinal positional markers, the protocol doesn’t allow for directly testing the caudalizing action of RA on ES-derived neural cells.
The induction of MN progenitors depends on Shh activity.
To activate the Shh signaling pathway, they used a specific small molecule agonist of Shh signalling, Hh-Ag1.3.
The generation of MNs in EBs depends on both the caudalizing action of RA and the ventralizing action of Sonic hedgehog (Shh).
Progenitors giving rise to MNs express Olig2, Nkx6.1, and low levels of Pax6.
Three steps of MN fate
Primary neuralization of ectodermal cells
Secondary caudalization of neural cells
Ventralization of caudalized neural cells
There’s evidence that the pathway of ES cell differentiation into MNs resembles the normal program involved in the caudalization and ventralization of neural cells.
ES cells can be neuralized by exposure to PA6 and can be further converted to a cervical spinal identity upon exposure to RA.
Findings support that RA promotes spinal fate in neuralized EBs that parallels its normal role in patterning the rostrocaudal axis of the neural tube.
The efficiency with which inductive signals are able to convert ES cells into MNs suggests a general strategy for generating other predefined classes of CNS neurons, through systematic variation in the identity and concentration of patterning signals to which ES cells are exposed.
The ability to direct cell fate solely through the use of extracellular factors, without the need to genetically manipulate ES cells, may allow a direct extension of this strategy to human ES cells and other classes of neural progenitor cells.
Week 3
Spinal Cord Injury Reveals Multilineage Differentiation of Ependymal Cells
Ependymal cells: cells that line the CNS and are involved in the production of CSF and is shown to serve as a reservoir for neuroregeneration.
Using genetic fate mapping, we show that close to all in vitro neural stem cell potential in the adult spinal cord resides within the population of ependymal cells lining the central canal.
Oligodendrocyte: the equivalent to Schwann cells but for the CNS and creates the myelin sheath around axons.
Paper shows that nearly all in vitro neural stem cell potential resides within the population of ependymal cells.
Summary
Identification of stem cells in the adult spinal cord opens up the possibility of manipulation of these cells to promote recovery after injury.
To identify such cells, the paper uses genetic tools to specifically address the identity and reaction to injury of a subpopulation of spinal cord cells known as ependymal cells.
Ependymal cells act as neural stem cells in vitro and contribute to the glial scar in vivo.
Results point to ependymal cells as an attractive candidate population for non-invasive manipulation after injury.
Ideas behind tamoxifen inducible cre/lox system
Used to map cell fate as it tags cells in the beginning and follows the cell’s divisions.
Two parts are used, the switch (CreER) and the reporter/promoter (lacZ).
The switch it activated by the metabolism result of tamoxifen, OHT, and results in the expression of B-gal.
By choosing the appropriate time window, dose, and frequency of tamoxifen treatment, cells of a particular type are irreversibly labeled.
The switch, when activated, acts as a pair of scissors that slices out the STOP sequence before the reporter and removes it, letting the cell read the reporter DNA section.
Once the STOP sequence is gone, the cell creates the reporter which is then observed to track cell fate.
Cre reporting allows inducible, permanent, and heritable genetic labeling.
The paper uses two promoters
FoxJ1: specific to cells possessing motile cilia/flagella aka ependymal cells.
Nestin: specific to CNS stem and progenitor cells. E.g. In the adult spinal cord, it’s expressed by cells lining the central canal, endothelial cells, and sparse white matter glial cells.
Figure 1
Shows using both (FoxJ1 and Nestin) transgenic lines of mice to label spinal cord Ependymal cells.
Compares CreER expression to Bgal to show that the majority of cells expressing CreER also express Bgal.
Figure 2
Shows characterization of spinal cord ependymal cells.
Three types
Cuboidal ependymal cell
Tanycyte
Radial ependymal cell
Adult spinal cord stem cells are largely contained within the Ependymal cell population.
Mice received five daily injections of tamoxifen to induce recombination (aka slicing out the STOP sequence).
Figure 3
Ependymal cells display neural stem cell properties in vitro.
Neurosphere: a culture system composed of free-floating clusters of neural stem cells.
Paper found that 100% of the recombined neurospheres from both Nestin-CreER and FoxJ1-CreER could be split at least eight times to give rise to new neurospheres.
Analysis of the differentiation potential of ependymal cell-derived neurospheres revealed that 100% of the neurosphere clones were multipotent and differentiated into neurons, astrocytes, and oligodendrocytes.
The neural stem cell potential in the adult spinal cord, within the paper’s context, largely lives within the ependymal cell population.
Ependymal cells self-renew in vivo and aren’t replenished by another cell population.
Figure 5
Ependymal cells are activated by spinal cord injury.
Ki67 immunoreactivity indicates ependymal proliferation in the injured but not the uninjured segment.
Ki-67 is an excellent marker to determine the growth fraction of a given cell population.
Sox3: ependymal cells
Sox9: neural stem cells
GFAP: astrocyte cells
Ependymal cells contribute to scar formation after injury.
Glial scar tissue is made up of two different populations of astrocyte-like cells, where the majority of Sox9 population derives from ependymal cells and the Nestin cells are mainly reactive resident astrocytes.
In addition to the generation of astrocytes, ependymal cells generate myelinating oligodendrocytes.
Ependymal cells are normally limited in proliferation but it increases dramatically after spinal cord injury.
Axonal regeneration is inhibited by scar formation and growth-inhibitory factors associated with myelin and astrocytes.
Week 4
Magnetic Vestibular Stimulation (MVS) As a Technique for Understanding the Normal and Diseased Labyrinth
Humans often experience dizziness and vertigo around strong static magnetic fields such as those in an MRI scanner.
Lorentz force: a combination of electric and magnetic force due to electromagnetic fields.
While in the MRI, the Lorentz force displaces the cupula of the lateral and anterior semicircular canals, as if the head was rotating with a constant acceleration.
Recording eye movements in an MRI shows a persistent nystagmus.
Nystagmus: when the eye makes repetitive, uncontrolled movements.
When the person exits the magnetic field, there is a transient aftereffect with the nystagmus beating in the opposite direction, reflecting adaptation.
MVS is useful for exploring set-point adaptation, the process by which the brain adapts to a change in its environment.
In an MRI machine, there’s a large static field that’s always active while high frequency oscillations in the magnetic field are only present when obtaining images.
Results
All normal human subjects tested had horizontal nystagmus while in the MRI
Direction of nystagmus reversed with extreme head pitch
Direction of nystagmus reversed with direction of entry
Effect showed some decay but was still present at 90 of stimulation
Effect didn’t depend on rate of motion into/out of the bore
Intensity of nystagmus scaled almost linearly with the strength of the magnetic field
No nystagmus was seen in patients with bilateral peripheral vestibular loss
Hypothesize that the nystagmus arose because of sustained pressure, transmitted via the endolymph fluid of the lateral semicircular canals, onto the cupula of the lateral semicircular canal.
Lorentz force generated from the interaction between the static magnetic field and the constant mechano-electrical transduction currents in the ion-rich endolymphatic fuild.
Vestibulo-ocular reflex (VOR)
Positioning the head in a null position might eliminate the MVS effect.
MVS is a relatively simple, safe, and novel way of stimulating the labyrinth.
MRI Magnetic Field Stimulates Rotational Sensors of the Brain
They use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (proportional to static magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation).
The vestibular labyrinth is the likely cause because after removing the labyrinth, animals don’t show abnormal postural responses due to magnetic fields.
The vestibulo-ocular reflex (VOR) links labyrinthine stimulation to eye movements.
Head rotation in one direction leads to eye rotation in the other, ensuring stable vision during head motion.
Nystagmus: an altering slow drift (slow phase) and fast resetting movement (quick phase) of the eyes.
Three possible explanations of MVS
Electromagnetic induction (EMI)
Magnetic susceptibility (MS)
Magnetohydrodynamics (MHD)
Paper uses the direction and velocity of the slow phases of nystagmus as a measure of the pattern of labyrinthine stimulation.
Subjects lay still in darkness and eye movements are measured using an infrared camera because visual cues are used by the brain to suppress unwanted nystagmus.
Two patients without functioning labyrinths developed no nystagmus, while all ten healthy subjects developed a robust nystagmus.
While inside the MRI bore, patients report a sense of rotation but this sensation often died away after a minute or so.
Nystagmus, however, persisted with the slow-phase velocity (SPV) slowly decreasing over minutes to a sustained level.
On leaving the bore, the nystagmus direction reversed and then gradually decayed over a few minutes.
Paper found that the magnitude and direction of the horizontal SPV were related to static head pitch position (chin up/down).
With increasingly downward chin positions, the SPV magnitude decreased, reached a null (no horizontal nystagmus), and eventually reversed and became rightward.
The null position differed among subjects, ranging from around -27 degrees to +32 degrees.
Eye movement data doesn’t correlate with EMI voltage, and they thus favor a static, non-EMI effect.
E.g. Increasing EMI voltage doesn’t change SPV but increasing the strength of the static magnetic field increases the SPV.
The reversal of SPV likely derives from adaptation to the persistent vestibular stimulation.
To rule out the MS mechanism, the MVS is polarity sensitive.
E.g. When the head was exposed to a magnetic field of opposite polarity, the nystagmus direction reversed.
Vertical nystagmus is produced when the head is tilted in the magnetic fields when the right/left ear to shoulder.
For the Lorentz hypothesis to be viable, there must be a source of continuous current within the inner ear.
Endolymph is an unusual extracellular fluid that’s high in potassium ions, which fills the internal chamber of the labyrinth.
Endolymph has two jobs
Carry ionic current for the mechanoelectrical transduction function of the vestibular hair cells.
Convey rotational force through each semicircular canal to its cupula (differential pressure sensor in the ampulla).
The Lorentz force is within the volume of endolymph fluid, not within the hair cells themselves.
This fluid force pushes against the cupula to stimulate its attached hair cells but doesn’t directly stimulate the hair cells.
The null position can vary as a result of anatomical variation of the utricle and ampulla.
Results have implications for understanding the effects of magnetic fields on the vestibular system and on the interpretation of fMRI/MRI studies.
Vestibular stimulation induced by the magnetic field could activate many brain areas related to vision, eye movements, and the perception of the position and motion of the body.
Implications
Effects could differ among subjects in 1.5, 3, and 7T magnets.
MVS is polarity sensitive which isn’t standardized among MRI manufacturers.
MVS could be a potential confound in studies.
MVS is a potentially noninvasive and comfortable way to stimulate the labyrinth for vestibular diagnosis.
Week 5
Effects of Location, Frequency Region, and Time Course of Selective Attention on Auditory Scene Analysis
To disentangled incoming auditory input into streams (each of which matches to a source), researchers have argued that the process is automatic and invariant. But recent evidence suggests that it’s affected by attention.
Experiments 1 and 2 show that attention isn’t a general suppression of streaming on the unattended side of the ascending auditory pathway or in unattended frequency regions.
Experiments 3 and 4 explore the effect on streams of physical gaps in the sequence and of brief switches in attention away from a sequence.
Results show that after even short gaps or brief switches in attention, streaming is reset.
Ways to disentangle audio input
Use prior knowledge of the target source.
Exploit regularities in natural sounds to group inputs into streams.
Previous experiments showed that an aspect of grouping previously thought to be low level and automatic is affected by whether the sounds are being attended to or not.
Study investigates the effect of selective attention on perceptual grouping.
Three hypotheses
Is attention required for the maintenance for stream segregation? It is required for stream buildup.
Does switching attention away from and back to a sequence instantly reset the percept to that of one stream?
Alternatively, does withdrawing attention cause stream segregation to decay at a rate with a time constant similar to its buildup?
Experiment 1
Use horse/morse to determine the number of streams heard.
Task 1: determine horse/morse.
Task 2: determine whether noise was increasing/decreasing.
Tones left and noises right, or tones and noises left.
Figure 3
On the two left-hand panels, we can clearly see that when the task was to perform task 1 throughout, stream segregation built up steadily from the start.
If the buildup of stream segregation were independent of attention, then we would expect the curves in the two right-hand panels to look like the latter half of the curves on the left.
If the buildup is dependent on attention, then we expect the curves on the right to look more similar to the first half of the curves on the left.
Buildup only begins when the stimuli are attended to.
Greater stream separation between high and low tones.
When attention is focused on a different set of sounds, there’s less buildup in auditory streaming.
Inhibition isn’t due to a general suppression of one ear, but rather of ear-specific parts of auditory cortex or of all sounds.
Early (1.5-4.5 s) and late (11.5-14.5 s)
Experiment 2
Test the effect of attention on the buildup of stream segregation is dependent on listeners attending to a different frequency region from the tones.
Same structure and procedure as experiment 1 but changed the stimuli so that the bandwidth of the noises encompassed the same frequency region as the tones.
Noise sounds in the distracting task (2) were filtered into a range that overlapped with tones.
The buildup of stream segregation was worse when attention was directed to a different set of sounds in the same frequency region, even if the sounds were in the same ear.
The effect of selective attention on stream segregation can also been seen even when there is strong overlap between the peripheral channels that are attended and the sounds on which streaming is measured.
Experiment 3
Test the effect of gaps in the sequence on stream segregation.
Does streaming decay or reset?
A short gap in a sequence resets the percept to one stream.
Results favor a resetting explanation and aren’t consistent with stream segregation decay.
Experiment 4
Three conditions
Continuous
As expected, with continuous tone sequences, there was substantial segregation throughout and little change.
Continuous-switch
The brief removal of attention reset the predominant initial percept to one stream to a similar extent as a physical gap.
Gap
The continuous tone was stopped for a period of time (gap) before resuming.
A brief switch in attention had an effect on perceptual grouping that was similar to the stimuli being switched off.
Either the maintenance of a segregated percept requires attention or the act of switching tones reset the perceptual grouping.
This paper confirms and extends Carlyon’s earlier finding that attention plays a crucial role in auditory stream segregation.
Irrelevant sound effect (ISE): where unattended auditory stimuli interfere with the serial recall of visually presented items.
Mismatch negativity (MMN): an EEG response that can be evoked to deviant stimuli among a series of standards even when listeners are instructed to ignore the sounds.
First two experiments explored whether the buildup of stream segregation happens around the currently attended location, frequency region, or only to the currently attended stream.
It was found that there was similar buildup whether the tone sequence and the distracting noises were in the same or in different ears, that there was little effect of whether they were in the same frequency region, and there was no interaction between these factors.
Results suggest a hierarchical decomposition model. It’s proposed that sound is decomposed into a partial hierarchy, with only attended branches fully elaborated.
Adding to the hierarchy that unattended branches aren’t elaborated/explored by the auditory system.
This preserves processing capacity. There might be limitations to how many simultaneous different firing patterns can be reliably coded without interference between them.
It would be extremely confusing if on a switch of attention from a voice, the immediately available auditory objects were small components of the other sound (E.g. The fret noise from a guitar) rather than the larger scale object of the music.
Week 6
When reviewing a manuscript, think about how you can improve the paper, not how to prevent it from publishing.
Hypothesis isn’t a prediction, it’s your best explanation of the phenomenon.
The prediction falls out of the hypothesis.
For an oral presentation, figure out the main message. Think of it like an hourglass, bottleneck the information.
A rationale that makes a hypothesis really solid.
When giving a presentation, don’t present, teach. Simplify and clarify.
Try not to have bulleted text in presentations.
Don’t read the presentation title (people can read it and it’s too technical), but still have a title slide.
At the start of two minutes, people are awake and aware. Don’t waste it by being technical.
Tell a story for a presentation.
To present rationale, open up the paper that inspired the current paper and use a figure from it.
Go slow, leave time for discussion. Repeat your main points. Leave some silence, especially after a main point.
Don’t mystify the reader/listener. Don’t use a term before defining it.
The goal is for the audience to understand you. Are you understood?
Email final assignment as a Word document for feedback.
Week 7
Rho Signaling Pathway Targeted to Promote Spinal Cord Repair
Rho signaling pathway plays an important role in neuronal growth inhibition.
Paper shows that inactivation of Rho or its downstream target Rho-associated kinase (ROK) stimulated neurite growth in primary cells of cortical neurons.
C3 inhibits Rho and Y27632 inhibits ROK and they’re sufficient to stimulate axon regeneration and recovery of hindlimb function after spinal cord injury (SCI) in adult mice.
Inactivation of Rho pathway induced rapid recovery of locomotion and progressive recuperation of forelimb-hindlimb coordination.
Findings provide evidence that Rho signaling pathway is a potential target for therapeutic interventions after spinal cord injury.
Chondroitin sulfate proteoglycan (CSPG): structural components for human tissues.
First tested whether treatment of neurons with C3/Y27632 was sufficient to stimulate growth on inhibitory substrates typical of the glial scar and white matter.
Figure 1
Neurons plated on CSPG, purified myelin, or a mixture of both did not extend long neurites and had a rounded shape.
After treatment with C3/Y27632, neurons were able to extend neurites.
C3 was significantly better than Y27632 in promoting neurite growth.
Important point is that the grey and black bars are much higher than the white bar.
Only axons that regenerate long distances show upregulation of GAP-43 mRNA expression.
High levels of GAP-43 mRNA expression in neurons of the motor cortex of C3-treated animals.
C3 treatments elicit changes in gene expression consistent with axon regeneration.
Failure of axon regeneration in the spinal cord is partially attributable to the growth inhibitory properties of white matter and the lesion site.
Both C3 and Y27632 promoted axon growth, but C3 was more effective than Y27632.
Difference between C3 and Y27632 suggest the presence of other effectors of Rho that are inactivated by C3 but not by Y27632.
Week 8
Evidence for holistic episodic recollection via hippocampal pattern completion
Paper provides evidence that the hippocampus binds together the diverse elements forming an event, allowing holistic recollection via pattern completion of all elements.
Participants learn complex ‘events’ from multiple overlapping pairs of elements, and are tested on all pairwise associations.
Results suggest that event elements, represented in distinct neocortical regions, are bound into coherent ‘event engrams’ in the hippocampus that enable episodic recollection, the re-experiencing of all aspects of an event, by a process of hippocampal pattern completion.
When retrieving an event, all aspects of an event are retrieved including contextual elements.
A widely held but long-debated view is that episodic memory is the key function of the hippocampus.
Pattern completion: the retrieval of all constituent elements of an event when presented with a single element as a cue.
Two key predictions
Statistical dependency for retrieval of different associations of the same event.
E.g. An event memory might bind together location, people, and objects. So a location cue should be related to the ability to retrieve the person and object.
Retrieval of any one element from an event should coincide with reactivation of neurons corresponding to all event elements (including those accompanying the task).
Couldn’t distinguish between the retrieval of events built across three separate trials and the retrieval of events learned on a single trial.
The key to creating holistically bound event representations lies in the associative structure created between the constituent elements.
Each trial is the presentation of one of the three possible pairwise associations from an event.
Closed-loop: all event elements are paired with all other elements.
Open-loop: elements of an event are presented as a chain of overlapping pairs.
Importantly, within-event dependency occurs for closed-loop but not open loop associative structures, allowing for testing the presence or absence of holistic retrieval.
Each event is tested across six trials.
Each model predicts the level of dependency expected if retrievals of elements from the same event are either independent or dependent, while controlling for factors such as the participant’s overall levels of performance and guessing.
The model shows the same pattern of dependency as seen in the behavioural data.
Paper’s computational model corroborates the interpretation that the different associative structures of the closed- versus open-loop events can give rise to pattern completion.
Open-loop events did not show behavioural dependency, whereas the closed-loop events did.
Behavioral dependency: the dependencies from the behavioral data and not the model data.
Week 9
Anatomically distinct dopamine release during anticipation and experience of peak emotion to music
Using PET scanning combined with psychophysiological measures of autonomic nervous system activity, authors found endogenous dopamine release in the striatum at peak emotional arousal during music listening.
The caudate was more involved during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses.
Results show that intense pleasure in response to music can lead to dopamine release in the striatal system and explains why music is of such high value across all human societies.
Humans have the ability to obtain pleasure from more abstract stimuli, such as music, art, and books, in contrast to pleasure from food and drugs.
Pleasure is a subjective phenomenon that’s difficult to assess objectively. However, physiological changes occur during moments of extreme pleasure that we can measure.
Paper uses the ‘chills’ response as a marker of peak emotional response and to objectively index pleasure.
Participants selected their own highly pleasurable music.
More binding potential = Less dopamine.
Psychophysiological measures
Heart rate
Respiration
Electrodermal skin conductance
Blood volume
Peripheral temperature
Second aim of the study was to explore the temporal dynamics of any dopaminergic activity.
E.g. Is dopamine release associated with the experience or the anticipation of the reward.
There was a significant positive correlation between the reported intensity of chills and the reported degree of pleasure.
Fig 1 further verifies that the chills response is a good objective representation of peak emotional arousal.
Fig 2 shows that the experience of pleasure while listening to music is associated with dopamine release in striatal reward systems.
Anticipation epochs were defined as 15s before the peak experiences.
Hemodynamic responses and dopamine activity were maximal in the caudate during anticipatory phases, but shifted more ventrally to nucleus accumbens (NAcc) during peak emotional responses.
The number of chills was significantly correlated with the right caudate, but not the NAcc.
The intensity of chills and the overall degree of pleasure experienced were most significantly correlated with the right NAcc, but not the caudate.
Paper provides the first direct evidence that the pleasure experienced when listening to music is associated with dopamine activity in the mesolimbic reward system, including the striatum.
It’s important to note that chills aren’t necessarily pleasurable but are markers of intense ANS arousal.
Week 10
Astrocyte Intermediaries of Septal Cholinergic Modulation in the Hippocampus
The authors describe a mechanism through which septohippocampal projections modulate the activity of hippocampal neurons.
Using a combination of optogenetics, in vivo and in vitro patch-clamp and single-unit recordings, and multiphoton imaging, the authors show that acetylcholine release from cholinergic septohippocampal projections causes a long-lasting GABAergic inhibition of hippocampal dentate granule cells.
This inhibition is caused by cholinergic activation of hilar astrocytes, which provide glutamatergic excitation of hilar inhibitory interneurons.
This constitutes a novel mechanism: acetylcholine release can cause slow inhibition of principal neuronal activity via astrocyte intermediaries.
It’s hypothesized that the release of acetylcholine (ACh) has an important role in mediating the interplay between encoding and retrieval.
Disruption of the cholinergic system leads to impaired memory.
Patch-clamp recordings from hippocampal dentate granule cells in anesthetized mice.
Within the dentate gyrus, cholinergic excitation is most marked in cells with dendrites within the hilar region.
FAc = Fluoroacetate = Inhibitory of glial metabolism.
Astrocytes don’t directly depolarize granule cells, but rather modulate presynaptic glutamate release onto granule cell dendrites.
Results suggest that ACh release inhibits both the recurrent CA3 networks and the inputs to the recurrent network from dentate gyrus.
Significant for the function of the dentate gyrus as a key relay governing information transfer from the entorhinal cortex into the hippocampal canonical circuit.
Week 11
Neural Activity in the Primate Prefrontal Cortex during Associative Learning
Results suggest that the prefrontal (PF) cortex has a role in rapidly forming and rearranging arbitrary associations.
Arbitrary stimulus-response associations.
E.g. Green = go and red = stop.
Paper explores the role of the PF cortex in arbitrary cue-response learning by studying the activity of lateral PF neurons during performance of a conditional visuomotor task.
By pairing each cue with each possible response, we can disambiguate the effects of the cue and the behavioral response.
Recorded from a total of 254 neurons in the left lateral PF of two monkeys.
Most of the neurons were responsive in at least one task period (cue, delay, choice).
48% showed activity of OBJECT but not DIRECTION.
29% showed activity of DIRECTION but not OBJECT.
60% showed activity of both OBJECT and DIRECTION.
The direction-selective activity observed could have been due to a “premotor” signal for the impending eye movement and/or a shift of visual attention preceding the eye movement.
Results indicate that PF neurons can integrate diverse, behaviorally relevant information.
Learning was reflected in PF activity by the earlier appearance of directionally selective activity within each trial.
Learning was also reflected in that most PF cells were activated more strongly by novel, reversing cues than by familiar, nonreversing cues.
