Electrophysiology

Slice and Cell

Electrophysiological data are a key component of our Database

Our cognitive skills are among the most amazing things in nature and we owe them to our brains. The human brain contains huge numbers of neurones and other types of brain cells, interconnected in an immensely complex network. All the information we receive about the outside world, as well as every conscious and subconscious mental reaction, is mediated by tiny electric currents that emerge and propagate among electrically-excitable neurones. Most of the neurones in the brain are joined together by specialised button-like contacts called synapses.

Synapses are formed between a presynaptic neurone, which sends a signal, and a postsynaptic neurone, which receives the signal. Synaptic transmission between two cells occurs when a presynaptic neurone becomes depolarised and as a consequence releases neurotransmitter molecules into the gap between the neurones, the synaptic cleft. Neurotransmitter molecules are contained in tiny vesicles, which fuse with the cell's outer membrane in response to the cell's depolarization and the subsequent influx of calcium into the presynaptic terminal. Once released from the cell in this way, the neurotransmitter molecules diffuse into the synaptic cleft and bind to receptors on the membrane of a postsynaptic neurone. Neurotransmitter binding leads to opening of receptor-coupled channels in the postsynaptic neurone, which in turn activates tiny electric currents through the membrane. These currents cause deflections of the otherwise stable resting membrane potential, known as postsynaptic potentials.

Depending on the nature of the neurotransmitter and receptor, postsynaptic potentials may either increase or decrease the probability of the postsynaptic neurone becoming excited. Excitatory receptors usually depolarize the membrane by allowing an influx of positively-charged ions into the cytoplasm. If a sufficient number of receptor-containing synapses are activated, a postsynaptic neurone may depolarize beyond a certain threshold and fire an action potential. At this point, a 'receiving' neurone may instead become a 'sender': its own presynaptic terminals become depolarized and release neurotransmitter, passing the signal on to other neurons to which it is connected.

The strength of the synaptic transmission may vary depending on the pattern of electric activity. Usually, an action potential in the presynaptic neurone would always evoke the same postsynaptic potential. However, episodes of intense neuronal activity, leading to excessive release of the neurotransmitter molecules, may lead to long-lasting changes in the relation between the activation of the pre- and postsynaptic neurons.

Following such episodes, a single action potential in the presynaptic neurone may evoke a consistently larger or smaller postsynaptic potential, leading to either long-term potentiation (LTP) or long-term depression (LTD) of the synaptic response. It appears that synapses can memorise unique patterns of their activation and change the responsiveness of their elements for hours and days. This ability of synapses to change the strength of communication through them is called synaptic plasticity.

There are good reasons to believe that the mechanisms underlying synaptic plasticity are important in the formation of memories. This is especially evident in the hippocampus, the part of the brain which is responsible for spatial memory. For example, deficiency in the activation of a particular type of postsynaptic receptors, called NMDA receptors, impairs synaptic plasticity in vitro and is also detrimental to spatial orientation of rodents in various behavioural tasks.

Electrophysiological properties such as synaptic plasticity can be studied either in brain slices or using cell cultures. Accordingly, G2C's Electrophysiology group is divided into the Slice and Cell teams.