Lecture on Synapse Structures and Functions

Introduction

  • Morning greeting and acknowledgment of students' efforts despite the cold.

  • Overview of lecture topics:

    • Revisiting synapse excitatory and inhibitory properties.

    • Discussing the selectivity of ion channels.

    • Exploring interactions between multiple synapses.

    • Complexity of the central nervous system (CNS).

Revisiting Synapse Types

  • Recap of concepts from the previous lecture:

    • Membrane depolarization due to cation influx results in excitatory postsynaptic potential (EPSP).

    • Outflow of cations or influx of anions leads to inhibitory postsynaptic potential (IPSP).

  • Essential question: What determines ion selectivity in ion channels?

Types of Ligand-Gated Ion Channels

  • Ligand-gated ion channels are categorized into three main families:

    1. Six-loop receptors:

    • Includes nicotinic acetylcholine receptors (nAChR), glycine receptors, GABA receptors.

    • Structure: Composed of pentameric structures with two transmembrane regions in each subunit.

    1. Glutamate receptors:

    • Subdivided into NMDA and AMPA receptors.

    • Structure: Each consists of four transmembrane regions including one loop that goes into and out of the membrane.

    1. P2X receptors:

    • ATP-sensitive receptors composed of trimeric structures.

    • Open channels upon ATP binding.

Importance of Structural Differences

  • Structural similarities among receptor families influence ion channel function:

    • Single amino acid sequence is encoded genetically, determining receptor properties.

    • Excitatory channels (nAChR, P2X) often have negative charges that attract positive ions.

    • Inhibitory channels (GABA, glycine) often possess positive charges that repel cations while attracting anions.

Testing Ion Channel Selectivity Hypotheses

  • Method to test ion selectivity:

    • Systematic mutation of amino acids in receptors (e.g., glycine receptor).

    • Specific amino acid mutations lead to alterations in ion selectivity from anion-selective to cation-selective channels.

    • Investigation focused on positions of critical charged amino acids in relation to receptor functions.

Understanding Postsynaptic Integration

  • Neurons typically receive simultaneous inputs:

    • Combinations of excitatory (EPSPs) and inhibitory (IPSPs) synaptic inputs.

    • Individual inputs usually change membrane potential only slightly (millivolts).

  • Effect of simultaneous activation of excitatory and inhibitory synapses:

    • The net effect is a balance that alters overall depolarization levels and may affect action potential generation.

Concept of Postsynaptic Inhibition

  • Definition: Synapses that stabilize the resting membrane potential below the action potential threshold.

    • Key scenario: If the reversal potential of an inhibitory synapse equals the resting potential, then no net current flow occurs upon activation.

  • Inhibitory Shunt:

    • When combined with excitatory inputs, even silent inhibitory inputs can reduce the excitability of postsynaptic cells by altering membrane resistance without changing potential directly.

Mechanisms of Inhibitory Synapses

  • Discussion on the significance of different ions:

    • Excitatory synapses typically allow cation flux (Na+, Ca+).

    • Inhibitory synapses often allow anion flux (Cl-), particularly in the case of GABA.

  • Significant consideration in understanding how inhibitory influences affect overall neuronal activity without direct observable changes in membrane potential.

Complexity of the Central Nervous System

  • Overview of CNS structural complexity:

    • Neurons are not isolated; they function within larger networks receiving thousands of synaptic inputs.

    • Recent advancements in neuroscience have reconstructed neural circuits revealing:

    • Individual neuron structures including dendritic trees.

    • Microscopic reconstructions of neuronal interactions within specified volumes of brain tissue (e.g. cortex).

  • Example data:

    • A single cubic millimeter of mouse cortex can consist of:

    • 200,000 cells, 75,000 neurons, and about 523 million synapses.

  • Scalability: Understanding that the human brain contains on the order of 100 billion neurons and more than funding of synapses.

Advances in Understanding Neuronal Connectivity

  • Methods used to record neuron activity and connectivity:

    • Technologies identifying relationships and interactions between different types of neurons (e.g., paired recordings).

    • Mapping connectivity from specific neuron activity to broader network responses.

  • Important concepts of:

    • Spatial integration: How multiple synapses interact to produce a combined effect.

    • Temporal integration: How repeated synaptic activity influences the neuron over time.

Conclusions from Today's Lecture

  • Summarized insights:

    • On selectivity in ligand-gated channels, roles of amino acid sequences, and the dynamics of inhibitory and excitatory postsynaptic potentials.

    • Complexity of neural networks and implications for understanding synaptic interactions and overall CNS function.

  • Mention of the focus in the next lecture on spatial and temporal integration dynamics.