Neuroscience 3600 Problem Set 4 Please Write Neatly And Give

Neuroscience 3600 Problem Set 4please Write Neatly And Give Complete

This assignment requires comprehensive and clear answers to various questions related to neuroscience, focusing on the electrical properties of neurons, synaptic mechanisms, neural circuitry, and neuropharmacology. The questions include comparisons of electrophysiological potentials, analysis of ion flow and membrane reversal potentials, experimental design to test neural projections, interpretation of electron micrographs, mechanisms of drug-enhanced neurotransmission, calculations of membrane potential changes, and analysis of synaptic inputs and ion channel functions. Students should synthesize theoretical knowledge with experimental data, emphasizing clarity, accuracy, and critical thinking in their responses.

Paper For Above instruction

The fundamental differences between excitatory postsynaptic potentials (EPSPs) and action potentials lie in their origin, mechanism, and significance in neuronal communication. EPSPs are localized, graded changes in the membrane potential caused primarily by the influx of sodium or calcium ions through ligand-gated channels upon neurotransmitter binding. They result in a depolarization that is proportional to the synaptic input and decay with distance from the synapse. Action potentials, in contrast, are all-or-none, regenerative events that propagate along the axon, initiated by reaching a critical threshold through cumulative EPSPs and inhibitory inputs. These are characterized by rapid depolarization and repolarization, involving voltage-gated sodium and potassium channels, with a duration typically around 1-2 milliseconds and a fixed amplitude of approximately +100 mV from resting potential.

EPSPs do not typically exhibit after-hyperpolarization, which is a feature associated primarily with action potentials. After-hyperpolarization results from specific voltage-gated potassium channels opening during the repolarization phase of an action potential, leading to a temporary undershoot below the resting potential. Since EPSPs are passive, graded responses mediated by ligand-gated ion channels, they fade with distance and time, and do not involve the same mechanisms that produce the after-hyperpolarization phase of an action potential.

The statement that the key determinant of whether a synapse is excitatory or inhibitory is the neurotransmitter is false. While the type of neurotransmitter (e.g., glutamate versus GABA) significantly influences synaptic nature, the ultimate effect—excitatory or inhibitory—depends on the specific ion channels activated and the ionic reversal potential relative to the resting membrane potential. For example, GABA typically causes inhibitory effects by opening chloride channels, leading to hyperpolarization if the chloride equilibrium potential is more negative than resting potential. Conversely, glutamate opens sodium and calcium channels, causing depolarization.

In experiments to determine the reversal potential of a synapse, the I-V plot illustrates how current changes with voltage. Using the approximate data, the reversal potential can be identified as the voltage where the current crosses zero. Based on the experimental results, this crossing occurs at about -50 mV, indicating the reversal potential for that synapse. The contributions of permeant ions are inferred from their relative permeabilities and equilibrium potentials. Potassium, with a high permeability and an equilibrium potential near -90 mV, contributes approximately 67% to the reversal potential. Sodium, with a permeability of 0.04 relative to potassium and an equilibrium potential of +60 mV, contributes about 3%. Chloride, with a permeability of 0.45 and an equilibrium potential near -70 mV, accounts for roughly 30%. To shift the reversal potential toward 0 mV, a manipulation like blocking potassium channels using tetraethylammonium (TEA) can be employed, as it reduces potassium conductance, making sodium and chloride conductances more dominant, thereby moving the reversal potential closer to 0 mV.

The dopaminergic projections from the ventral tegmental area (VTA) to the medial prefrontal cortex (mPFC) and striatum are critical in decision making and reward processing. To distinguish between the hypotheses of collateral projections from a single VTA neuron population versus separate distinct populations, a genetic or anatomical tracing approach can be employed. Using retrograde tracers injected specifically into the mPFC and striatum, combined with immunohistochemistry for dopamine neurons, one can determine if the same VTA neurons project to both regions. Alternatively, optogenetic activation of VTA neurons combined with recordings from mPFC and striatal neurons can reveal whether stimulating a subset of VTA neurons affects both areas simultaneously or if separate subsets innervate the regions independently. Overlapping projections would support the collateral hypothesis, while distinct projections would support the separate populations hypothesis.

The electron micrograph showing axon and dendrites displays unusual characteristics. The presence of clusters of polyribosomes in dendrites indicates active local protein synthesis, which is typical for dendritic shafts involved in synaptic plasticity. However, the description of a short, thin axon suggests abnormal morphology, possibly indicative of degeneration or developmental immaturity. Normal axons tend to be thicker, with fewer ribosomes, and are specialized for reliable transmission. The presence of ribosomal clusters in dendrites confirms their neuron-like function, but in the axon, this is abnormal, potentially reflecting degenerative processes or aging-related changes that impair efficient communication.

Three mechanisms by which drugs or toxins can enhance neurotransmission include: (1) increasing neurotransmitter release, exemplified by amphetamines which promote the release of dopamine into the synaptic cleft, (2) inhibiting neurotransmitter breakdown, such as monoamine oxidase inhibitors (MAOIs) that increase levels of serotonin, norepinephrine, and dopamine by blocking their degradation, and (3) blocking presynaptic or postsynaptic reuptake transporters. For example, cocaine inhibits dopamine reuptake, prolonging its action in the synaptic cleft, thereby enhancing dopaminergic transmission. Each mechanism increases synaptic concentration of neurotransmitters, amplifying their effect on postsynaptic neurons and modulating neural signaling.

The membrane potential (Em) of a postsynaptic neuron depends on the conductance and reversal potential of various ion channels activated during synaptic transmission. Given the parameters, the EPSP without inhibition can be calculated as a weighted average of the resting potential and the excitatory reversal potential: Em ≈ -65 + (2 x (–10 – (–65))) / (1 + 2) ≈ +36.3 mV. When an inhibitory conductance is also engaged, the net potential tends toward the inhibitory reversal potential, resulting in an Em ≈ -65 + (1 x (–70 – (–65))) / (1 + 2) ≈ +23.3 mV. The combined effect of EPSP and IPSP produces a peak voltage change summed algebraically, approximately +59.5 mV, but the net potential during simultaneous activation is less than the arithmetic sum (~134.6 mV) due to the non-linear integration of conductances and the overall electrochemical driving forces.

Considering two neighboring synapses that produce +18 mV depolarizations from a resting potential of -80 mV to a threshold of -40 mV, the total combined depolarization (36 mV) is insufficient to reach the threshold. Since the combined depolarization still leaves the membrane potential at -62 mV (if summed linearly), it does not exceed the -40 mV threshold necessary for spike initiation. Therefore, these two synapses alone cannot reliably evoke a postsynaptic action potential under these conditions, illustrating the importance of temporal summation or additional synaptic inputs for spike generation.

Initially, in the presence of equal permeability to Na+ and K+, the ionic currents during an EPSP include inward Na+ and outward K+ flows. Under conditions where Na+ concentrations are equal inside and outside, the driving force for Na+ influx diminishes, nearly eliminating Na+ current contribution since the electrochemical gradient is abolished. Consequently, the EPSP would be dominated by K+ conductance, resulting in reduced depolarization magnitude and a shift of the current flow. This change reduces the efficacy of excitatory synaptic transmission, emphasizing the importance of concentration gradients and ion-specific permeability in shaping neuronal responses.

References

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  • Huang, Y., et al. (2017). Pharmacological enhancement of neurotransmission: mechanisms and implications. Trends in Pharmacological Sciences, 38(9), 725-738.
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