Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study.

Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

Depolarizing/hyperpolarizing effects of the GABA(A) synapse have a beneficial role in synaptic weight resetting in the hippocampus.

To eliminate undesirable memory traces from the short-term memory system, it is a crucial question to reorganize the activity induced synaptic efficiency. Here we suggest a possible solution for this mechanism. In the first part of the paper we demonstrate, that under different physiological conditions even in the case of adult animals, the GABA(A) synapse may mediate a depolarizing effect on the membrane potential. Considering the GABA(A) receptor-mediated complex effects on the membrane potential of adult mammalian central neurons we raised the question of the properties of the network, which has elements in the synaptic weight matrix with changing signs. The second part pinpoints the beneficial learning ability of such a network.

Single cell and population activities in cortical-like systems.

Dynamics of single cells and large cell populations are the subject of investigation by using differently detailed models. Multicompartmental modeling techniques are used to systematically investigate the location-dependent effects of GABA-ergic inhibition on the firing patterns of hippocampal pyramidal cells. Appearance of stochastic resonance in a model of mitral and granule cells of the olfactory bulb is demonstrated by using a single-compartmental model approach. Spatial propagation of synchronized activities in hippocampal slices are studied by a model of large neural populations.