Synaptic Integration in the Visual Cortex

Sacha Nelson
Assistant Professor of Biology

Neurons in the visual cortex respond selectively to particular features or patterns in the visual world. The objective of our research is to understand the cellular and circuit-level properties that underlie this selectivity.

We employ two approaches to this problem: a "bottom-up" approach in which we try to understand the basic cellular and synaptic building blocks of corticalfunction in an in vitro slice preparation, and a "top-down" approach in which we study the responses of neurons to sensory stimuli in vivo.

One set of questions concerns the way in which successive synaptic inputs are integrated over time. We have found several forms of short-term synapticplasticity which may underlie motion perception and the adaptation to visual stimuli observed in vivo.

Another set of questions concerns spatial aspects of synaptic integration. Recently we used whole cell electrodes to introduce selective blockers of inhibitioninto single cortical neurons in vivo while recording their synaptic responses to oriented bars of light. The results indicate that selectivity arises primarilyfrom the convergence of excitatory inputs rather than on inhibition of responses to non optimal stimuli.

As a compliment to these experimental approaches, we have also been collaborating on models of the visual cortex, both at the single cell level, in order todetermine how the structure of neurons affects their integrative properties, and at the network level, in order to understand how selectivity may arise throughcooperative interactions between large numbers of cortical neurons.

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Plasticity and Stability in Cortical Networks

Gina Turrigiano
Assistant Professor of Biology

During learning and development, neural circuitry is refined through changes in the number and strength ofsynapses. Most studies of long-term changes in synaptic strength have concentrated on "Hebbian" mechanisms,where correlated firing changes synaptic strengths in a synapse-specific manner. While Hebbian mechanisms are important for selectively modifying neuronal circuitry, they may not be sufficient, because they tend to destabilizethe activity of neuronal networks. Recently my lab has identified several novel forms of homeostatic synaptic plasticity that stabilize the properties of cortical circuits. These include mechanisms that regulate neuronal excitability, stabilize total synaptic strength, and influence the balance of cortical excitation and inhibition. Theseforms of homeostatic plasticity are likely to be essential counterparts to Hebbian plasticity, that together allow activity to selectively modify the properties of cortical networks.

We wish to understand how changes in neuronal activity are translated into a set of coordinated changes insynaptic strength at many sites in a complex neuronal network. The neurotrophin BDNF appears to play a keyrole in this process; levels of this neurotrophin are regulated by activity, and we have shown that BDNF regulates the strength of synaptic connections between cortical neurons. An interesting aspect of this regulation is thatBDNF has very different effects on different classes of cortical synapse. Our data suggest that when activity (and BDNF levels) rise, synaptic strengths are regulated to lower pyramidal neuron firing rates and raise interneuronalfiring rates, whereas when activity (and BDNF levels) fall, synaptic strengths are regulated to increase pyramidalneuron firing rates and lower interneuronal firing rates. This suggests that an important role for thisneurotrophin in cortex is to regulate the balance of excitation and inhibition.

Measurement of miniature excitatory postsynaptic currents (mEPSCs)from cultured cortical pyramidal neurons grown under control conditions (Control), conditions of activity blockade (TTX), or conditions of activity enhancement (bicuculline). 48 hours of Activity blockade increases the amplitude of mEPSCs, whereas 48 hours of enhanced activity decreasesmEPSC amplitude.