The common preconception about central nervous system neurones is that thousands of small postsynaptic potentials sum across the entire dendritic tree to generate substantial firing rates, previously observed in in vivo experiments. We present evidence that local inputs confined to a single basal dendrite can profoundly influence the neuronal output of layer V pyramidal neurones in the rat prefrontal cortical slices. In our experiments, brief glutamatergic stimulation delivered in a restricted part of the basilar dendritic tree invariably produced sustained plateau depolarizations of the cell body, accompanied by bursts of action potentials. Because of their small diameters, basolateral dendrites are not routinely accessible for glass electrode measurements, and very little is known about their electrical properties and their role in information processing. Voltage-sensitive dye recordings were used to follow membrane potential transients in distal segments of basal branches during sub-and suprathreshold glutamate and synaptic stimulations. Recordings were obtained simultaneously from multiple dendrites and multiple points along individual dendrites, thus showing in a direct way how regenerative potentials initiate at the postsynaptic site and propagate decrementally toward the cell body. The glutamate-evoked dendritic plateau depolarizations described here are likely to occur in conjunction with strong excitatory drive during so-called 'UP states', previously observed in in vivo recordings from mammalian cortices. Several lines of evidence suggest that basal dendrites play a very important role in cortical information processing. Studies that combine physiological and histological techniques have shown that connections between layer V large pyramidal cells are mediated by synaptic junctions placed mainly on the basal dendrites (Deuchars et al. 1994;Markram et al. 1997). Local excitatory contacts are essential in a process known as 'recurrent excitation' , which is thought to be the cellular substrate of persistent neuronal activity (Goldman-Rakic, 1995;Compte et al. 2000;Goldman et al. 2003). Basal and proximal oblique dendrites are ideally suited to participate in recurrent excitation in that they comprise approximately twothirds of the total membrane area of a neurone. Based on dendritic spine counts, it has been estimated that This paper is dedicated to the memory of Patricia Goldman-Rakic, our dear friend and colleague.within the boundaries of layer V, basal and oblique branches receive approximately 65% of the total number of excitatory synaptic contacts (Larkman, 1991). Interestingly, Lucifer yellow injections showed that those cortical pyramidal neurones, which exhibit UP and DOWN states in vivo, have noticeably rich basal dendritic arbors (Steriade et al. 1993a). In vitro models of cortical rhythmic recurrent activity unequivocally showed that synaptic inputs arriving on basal and proximal oblique dendrites within the boundaries of layers V and VI are the major source of excitatory drive during the UP s...

One of the fundamental problems in neurobiology is to understand the cellular mechanism for sustained neuronal activity (neuronal UP states). Prefrontal pyramidal neurons readily switch to a long-lasting depolarized state after suprathreshold stimulation of basal dendrites. Analysis of the dendritic input-output function revealed that basal dendrites operate in a somewhat binary regimen (DOWN or UP) in regard to the amplitude of the glutamate-evoked electrical signal. Although the amplitude of the dendritic potential quickly becomes saturated (dendritic UP state), basal dendrites preserve their ability to code additional increase in glutamatergic input. Namely, after the saturation of the plateau amplitude, an additional increase in excitatory input is interpreted as an increase in plateau duration. Experiments performed in tetrodotoxin indicate that the maintenance of a stable depolarized state does not require inhibitory inputs to "balance" the excitation. In the absence of action potential-dependent (network-driven) GABAergic transmission, pyramidal neurons respond to brief (5 ms) glutamate pulses with stable long-lasting (~500 ms) depolarizations. Voltage-sensitive dye recordings revealed that this somatic plateau depolarization is precisely time-locked with the regenerative dendritic plateau potential. The somatic plateau rises a few milliseconds after the onset of the dendritic transient and collapses with the breakdown of the dendritic plateau depolarization. In our in vitro model, the stable long-lasting somatic depolarization (UP state like) is a direct consequence of the local processing of a strong excitatory glutamatergic input arriving on the basal dendrite. The slow component of the somatic depolarization accurately mirrors the glutamate-evoked dendritic plateau potential (dendritic UP state).

AK, Marks JD, van Drongelen W. Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents. J Neurophysiol 115: 3073-3089, 2016. First published March 16, 2016 doi:10.1152/jn.00995.2015.-The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while shorttimescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Na p ) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABA A , AMPA, and NMDA receptors and riluzole to selectively block Na p channels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABA A ϩ NMDA ϩ AMPA, NMDA ϩ AMPA, GABA A ϩ AMPA, GABA A ϩ NMDA, AMPA, NMDA, GABA A , and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Na p currents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties. epilepsy; multielectrode arrays; network bursting; pharmacology; synaptic mechanisms SPONTANEOUS NETWORK-WIDE SYNCHRONIZED bursting activity appears to play an important role in several aspects of the nervous system including development (Gu and Spitzer 1995;Meister et al. 1991;Shatz 1990;Yuste et al. 1992) and integration in the sensory system (Engel et al. 1992) but also in the initiation of pathological activity such as epileptic seizures (Gutnick et al. 1982;Miles and Wong 1983). Therefore, clarifying how the underlying synaptic and intrinsic neuronal properties modulate and cause this network behavior is likely to provide valuable under...

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