Faculty Opinions recommendation of Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle.

Author(s):  
Leonard Maler
2000 ◽  
Vol 84 (5) ◽  
pp. 2398-2408 ◽  
Author(s):  
Nathan P. Staff ◽  
Hae-Yoon Jung ◽  
Tara Thiagarajan ◽  
Michael Yao ◽  
Nelson Spruston

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance ( R N), membrane time constant (τm), and depolarizing “sag” in response to hyperpolarizing current pulses were similar in all subicular neurons, while R N and τm were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.


2011 ◽  
Vol 106 (5) ◽  
pp. 2216-2231 ◽  
Author(s):  
Patrick L. Sheets ◽  
Benjamin A. Suter ◽  
Taro Kiritani ◽  
C. Savio Chan ◽  
D. James Surmeier ◽  
...  

Motor cortex is a key brain center involved in motor control in rodents and other mammals, but specific intracortical mechanisms at the microcircuit level are largely unknown. Neuronal expression of hyperpolarization-activated current ( Ih) is cell class specific throughout the nervous system, but in neocortex, where pyramidal neurons are classified in various ways, a systematic pattern of expression has not been identified. We tested whether Ih is differentially expressed among projection classes of pyramidal neurons in mouse motor cortex. Ih expression was high in corticospinal neurons and low in corticostriatal and corticocortical neurons, a pattern mirrored by mRNA levels for HCN1 and Trip8b subunits. Optical mapping experiments showed that Ih attenuated glutamatergic responses evoked across the apical and basal dendritic arbors of corticospinal but not corticostriatal neurons. Due to Ih, corticospinal neurons resonated, with a broad peak at ∼4 Hz, and were selectively modulated by α-adrenergic stimulation. Ih reduced the summation of short trains of artificial excitatory postsynaptic potentials (EPSPs) injected at the soma, and similar effects were observed for short trains of actual EPSPs evoked from layer 2/3 neurons. Ih narrowed the coincidence detection window for EPSPs arriving from separate layer 2/3 inputs, indicating that the dampening effect of Ih extended to spatially disperse inputs. To test the role of corticospinal Ih in transforming EPSPs into action potentials, we transfected layer 2/3 pyramidal neurons with channelrhodopsin-2 and used rapid photostimulation across multiple sites to synaptically drive spiking activity in postsynaptic neurons. Blocking Ih increased layer 2/3-driven spiking in corticospinal but not corticostriatal neurons. Our results imply that Ih-dependent synaptic integration in corticospinal neurons constitutes an intracortical control mechanism, regulating the efficacy with which local activity in motor cortex is transferred to downstream circuits in the spinal cord. We speculate that modulation of Ih in corticospinal neurons could provide a microcircuit-level mechanism involved in translating action planning into action execution.


Science ◽  
2009 ◽  
Vol 325 (5941) ◽  
pp. 756-760 ◽  
Author(s):  
M. E. Larkum ◽  
T. Nevian ◽  
M. Sandler ◽  
A. Polsky ◽  
J. Schiller

Author(s):  
Xiao-Jing Wang

The prefrontal cortex (PFC) circuits are characterized by several distinct features. First, the input–output connections of a PFC circuit with the rest of the brain are extraordinarily extensive. In the primates, pyramidal neurons in PFC are greatly more spinous than in the primary sensory areas, so they have a much larger capacity for synaptic integration. Second, PFC areas are endowed with strong intrinsic recurrent connections that are sufficient to generate reverberatory activity underlying working memory and decision-making. Third, excitation and inhibition are balanced dynamically. Unlike early sensory cortical areas, in the frontal areas of both monkey and mouse, the synaptic inhibitory circuit is predominated by GABAergic cell subclasses that are dedicated to controlling inputs to, rather than outputs from, pyramidal neurons, likely reflecting the functional demand of selectively gating input pathways into the PFC in accordance with the behavioral context and goals.


1999 ◽  
Vol 82 (6) ◽  
pp. 3268-3285 ◽  
Author(s):  
David B. Jaffe ◽  
Nicholas T. Carnevale

We examined how biophysical properties and neuronal morphology affect the propagation of individual postsynaptic potentials (PSPs) from synaptic inputs to the soma. This analysis is based on evidence that individual synaptic activations do not reduce local driving force significantly in most central neurons, so each synapse acts approximately as a current source. Therefore the spread of PSPs throughout a dendritic tree can be described in terms of transfer impedance ( Zc ), which reflects how a current applied at one location affects membrane potential at other locations. We addressed this topic through four lines of study and uncovered new implications of neuronal morphology for synaptic integration. First, Zc was considered in terms of two-port theory and contrasted with dendrosomatic voltage transfer. Second, equivalent cylinder models were used to compare the spatial profiles of Zc and dendrosomatic voltage transfer. These simulations showed that Zc is less affected by dendritic location than voltage transfer is. Third, compartmental models based on morphological reconstructions of five different neuron types were used to calculate Zc , input impedance ( ZN ), and voltage transfer throughout the dendritic tree. For all neurons, there was no significant variation of Zc with location within higher-order dendrites. Furthermore, Zc was relatively independent of synaptic location throughout the entire cell in three of the five neuron types (CA3 interneurons, CA3 pyramidal neurons, and dentate granule cells). This was quite unlike ZN , which increased with distance from the soma and was responsible for a parallel decrease of voltage transfer. Fourth, simulations of fast excitatory PSPs (EPSPs) were consistent with the analysis of Zc ; peak EPSP amplitude varied <20% in the same three neuron types, a phenomenon that we call “passive synaptic normalization” to underscore the fact that it does not require active currents. We conclude that the presence of a long primary dendrite, as in CA1 or neocortical pyramidal cells, favors substantial location-dependent variability of somatic PSP amplitude. In neurons that lack long primary dendrites, however, PSP amplitude at the soma will be much less dependent on synaptic location.


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