I missed the beginning of Bruce Hope's presentation who was talking about electrophysiological changes in accumbal neurons after repeated cocaine exposure, so I wasn't able to follow the rest of the talk.

Next up was Garret Stuber who is using optogenecis to study natural rewards in mice. Nucleus accumbens (NA) neurons receive dopaminergic input from the ventral tegmental area (VTA) and glutamatergic input from the amygdala, mPFC and hippocampus. Local interneurons are cholinergic. NA neurons can be divided into thse with a D1 receptor and those expressing D2 receptors. Garret's lab uses optogenetics (channelrhodopsin) to drive activity in projection neurons in the basolateral amygdala (BLA). These projection neurons target the NA and if they shine light (using chronically implanted light guides) onto the NA where these projection neurons terminate, they can elicit spikes in the postsynaptic NA neurons. Mice readily learn to nose-poke for such light-induced BLA to NA stimulation, indicating reinforcing properties of this connection. Interestingly, these reinforcing properties are dopamine-dependent, mediated by D1 receptors. He didn't mention where this dopamine would be coming from, given that the projection neurons he was targeting were glutamatergic and I don't know why he didn't first use a glutamate antagonist to see of that would block the reinforcing properties of the light stimulus (upon my question he said that they has done it and that the antagonist had not eliminated but strongly attenuated self-stimulation). They also expressed halorhodopsin in these BLA projection neurons, leading to an inhibition of these neurons upon light stimulation. They used a classical conditioning paradigm to test the effects of this inhibition. Inhibiting these neurons with light during CS presentation prevented acquisition of the conditioned response. They also transfected mPFC neurons with channelrhodopsin. This mPFC to NA connection is not reinforcing. One reason may be that this connection releases less glutamate in the NA, but I did not have the impression they know a lot of what is going on there, yet.

Next up was Gwendolyn Calhoon looking at spontaneous activity in medium spiny neurons (MSNs) in the ventral striatum. This spontaneous firing is called the 'up-state' of the neurons, while silent MSNs are in the 'down-state'. MSNs in the down-state are not only generally silent, they are also very difficult to activate. One may then hypothesize that the transition between up- and down-states functions as a gate to allow input to propagate through the striatum. In her experiments, Gwendolyn is looking at NA MSNs receiving input from mPFC and hippocampus. She finds that mPFC input to these neurons can block transmission of hippocampal input, as long as the mPFC and hippocampal input arrive sufficiently close in time (first mPFC then hippocampus at 50 ms). The mPFC input needs to come in a high-frequency train in order to be able to block the hippocampal response in the MSNs. She found similar results when replacing hippocampal input with thalamus input. This inhibitory effect is specific to mPFC input, as reversing the protocol such that a train of input from the hippocampus precedes mPFC input, has no blocking effect. The mPFC-mediated suppression of hippocampal input is dependent on GABA-a receptors.

Final speaker in this morning session was Michael Cohen talking about electrophysiological experiments in humans. The focus of his research lies in the medial frontal cortex (MFC). His main techniques are EEG and MEG. He finds that negative performance feedback increases MFC oscillations in the theta range. He also used deep brain stimulation of the NA as a treatment option for depression and obsessive-compulsive disorder. Besides being an effective treatment, the researchers also use the implantation for some basic research, by using the stimulation electrodes as recording electrodes for several days between two subsequent surgeries. These electrodes can only record the local field potentials at the location of the electrode. They subject the patients to a reversal learning paradigm where one cue is first associated with reward while another is not and then the roles of the cues are reversed. Reversal learning is often used as a measure of behavioral flexibility. There occurs negative performance feedback in these experiments and they find that theta-band oscillatory synchronization between the two NAs was strongest for trials in which the patients received such negative feedback, dovetailing with the MFC EEG results (the MFC is providing input to the NA). This data can be interpreted as a shift from regional synchronization to more global synchronization after negative feedback. This hypothesis is supported by an increase in MFC-NA synchrony after negative feedback as measured by a combination of EEG with deep electrode recording. The same technique was used in a different behavioral paradigm, where the patients were asked to press a button as quickly as possible, but have been signaled whether or not this press will lead to a reward or not. A large caveat of these studies is that all of these experiments are performed on patients, meaning that something in thier brain is not functioning properly and it is difficult to know how the disorder is influencing the results obtained. Therefore, a combination of two noninvasive techniques in healthy subjects is preferred: EEG with MRI. The used EEG to determine a seed region in the brain which is likely to be responsible for the recorded EEG activity. The seed region was then used in MRI to study the connectivity of this seed region with other brain regions. They found that fronto-striatal connectivity supports error-related theta activity recorded by EEG.