During development, sensory systems switch from an immature to an adult mode of function along with the emergence of the active cortical states. Here, we used patch-clamp recordings from neocortical slices in vitro to characterize the developmental changes in the basic electrophysiological properties of excitatory L4 neurons and their connectivity before and after the developmental switch, which occurs in the rat barrel cortex in vivo at postnatal day P8. Prior to the switch, L4 neurons had higher resting membrane potentials, higher input resistance, lower membrane capacity, as well as action potentials (APs) with smaller amplitudes, longer durations and higher AP thresholds compared to the neurons after the switch. A sustained firing pattern also emerged around the switch. Dual patch-clamp recordings from L4 neurons revealed that recurrent connections between L4 excitatory cells do not exist before and develop rapidly across the switch. In contrast, electrical coupling between these neurons waned around the switch. We suggest that maturation of electrophysiological features, particularly acquisition of a sustained firing pattern, and a transition from the immature electrical to mature chemical synaptic coupling between excitatory L4 neurons, contributes to the developmental switch in the cortical mode of function.

The excitatory action of gamma-aminobutyric acid (GABA) is considered to be a hallmark of the developing nervous system. However, in immature brain slices, excitatory GABA actions may be secondary to neuronal injury during slice preparation. Here, we explored GABA actions in the rodent intact hippocampal preparations and at different depths of hippocampal slices during the early post-natal period [post-natal days (P) 1–7]. We found that in the intact hippocampus at P1–3: (i) GABA exerts depolarizing action as seen in cell-attached single GABA(A) channel recordings; (ii) GABA(A) receptor (GABA(A)-R) agonist isoguvacine and synaptic activation of the GABA(A)-Rs increase the frequency of multiple unit activity and the frequency of the network-driven giant depolarizing potentials (GDPs); and that (iii) Na+–K+–2Cl- cotransporter (NKCC1) antagonist bumetanide suppresses GDPs and the excitatory actions of isoguvacine. In the hippocampal slices at P2–5, isoguvacine and synaptic activation of GABA(A)-Rs-evoked excitatory responses at all slice depths, including surface and core. Thus, GABA exerts excitatory actions in the intact hippocampus (P1–3) and at all depths of hippocampal slices (P2–5). Therefore, the excitatory actions of GABA in hippocampal slices during the first post-natal days are not due to neuronal injury during slice preparation, and the trauma-related excitatory GABA actions at the slice surface are a fundamentally different phenomenon observed during the second post-natal week.

Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAB receptors. We also showed that LTD at this synaptic connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect, CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation.

Long-term potentiation and depression of synaptic transmission have been considered as cellular mechanisms of memory in studies conducted in recent decades. These studies were predominantly focused on mechanisms underlying plasticity at excitatory synapses. Nevertheless, normal central nervous system functioning requires maintenance of a balance between inhibition and excitation, suggesting existence of similar modulation of glutamatergic and GABAergic synapses. Here we review the involvement of G-protein-coupled receptors in the generation of long-term changes in synaptic transmission of inhibitory synapses. We considered the role of endocannabinoid and glutamate systems, GABA and opioid receptors in the induction of long-term potentiation and long-term depression in inhibitory synapses. The pre- and postsynaptic effects of activation of these receptors are also discussed.

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