Characterization of intracortical synaptic connections in the mouse anterior cingulate cortex using dual patch clamp recording

The anterior cingulate cortex (ACC) is involved in sensory, cognitive, and executive functions. Studies of synaptic transmission and plasticity in the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions. Previous anatomic studies suggest complex local interactions among neurons within the ACC. However, there is a lack of functional studies of such synaptic connections between ACC neurons. In the present study, we characterized the neuronal connections in the superficial layers (I-III) of the mouse ACC using dual whole-cell patch clamp recording technique. Four types of synaptic connections were observed, which are from a pyramidal neuron to a pyramidal neuron, from a pyramidal neuron to an interneuron, from an interneuron to a pyramidal neuron and from an interneuron to an interneuron. These connections exist among neurons in layer II/III or between neurons located layer I and II/III, respectively. Moreover, reciprocal connections exist in all four types of paired neurons. Our results provide the first key evidence of functional excitatory and inhibitory connections in the ACC

Remarks on the number of tubulin dimers per neuron and implications for Hameroff-Penrose Orch OR

Stuart Hameroff has wrongly estimated that a typical brain neuron has 10^7^ tubulin dimers and wrongly attributed this result to Yu and Baas, J. Neurosci. 1994; 14: 2818-2829. In this letter we show that Hameroff’s estimate is based on misunderstanding of the results provided by Yu and Baas, who actually measured the total microtubule length in a single axonal projection with length of 56 μm in a differentiating in vitro stage 3 embryonic hippocampal neuron. In order to visualize how big Hameroff’s error is, we have reconstructed two of the studied by Yu and Baas embryonic hippocampal neurons with Neuromantic v1.6.3 and compared them with previously published reconstructions of adult hippocampal neurons. Correct calculations show that an adult differentiated pyramidal neuron in vivo has approximately 1.3×10^9^ tubulin dimers incorporated in cytoskeletal microtubules. This estimate has profound implications for the Hameroff-Penrose Orch OR model, because it sets limitations on the number of quantum coherent neurons and implies that if 100% of the neuronal microtubules are quantum coherent for 25 ms then Hameroff-Penrose Orch OR conscious events should involve only 15 pyramidal neurons

The Spatial Structure of Stimuli Shapes the Timescale of Correlations in Population Spiking Activity

Throughout the central nervous system, the timescale over which pairs of neural spike trains are correlated is shaped by stimulus structure and behavioral context. Such shaping is thought to underlie important changes in the neural code, but the neural circuitry responsible is largely unknown. In this study, we investigate a stimulus-induced shaping of pairwise spike train correlations in the electrosensory system of weakly electric fish. Simultaneous single unit recordings of principal electrosensory cells show that an increase in the spatial extent of stimuli increases correlations at short (~10 ms) timescales while simultaneously reducing correlations at long (~100 ms) timescales. A spiking network model of the first two stages of electrosensory processing replicates this correlation shaping, under the assumptions that spatially broad stimuli both saturate feedforward afferent input and recruit an open-loop inhibitory feedback pathway. Our model predictions are experimentally verified using both the natural heterogeneity of the electrosensory system and pharmacological blockade of descending feedback projections. For weak stimuli, linear response analysis of the spiking network shows that the reduction of long timescale correlation for spatially broad stimuli is similar to correlation cancellation mechanisms previously suggested to be operative in mammalian cortex. The mechanism for correlation shaping supports population-level filtering of irrelevant distractor stimuli, thereby enhancing the population response to relevant prey and conspecific communication inputs. © 2012 Litwin-Kumar et al

The Enigmatic Function of Chandelier Cells

Chandelier (or axo-axonic) cells are one of the most distinctive GABAergic interneurons in the brain. Their exquisite target specificity for the axon initial segment of pyramidal neurons, together with their GABAergic nature, long suggested the possibility that they provide the ultimate inhibitory control of pyramidal neuron output. Recent findings indicate that their function may be more complicated, and perhaps more interesting, than initially believed. Here we review these recent developments and their implications. We focus in particular on whether chandelier cells may provide a depolarizing, excitatory effect on pyramidal neuron output, in addition to a powerful inhibition

How feedback inhibition shapes spike-timing-dependent plasticity and its implications for recent Schizophrenia models

It has been shown that plasticity is not a fixed property but, in fact, changes depending on the location of the synapse on the neuron and/or changes of biophysical parameters. Here we investigate how plasticity is shaped by feedback inhibition in a cortical microcircuit. We use a differential Hebbian learning rule to model spike-timing dependent plasticity and show analytically that the feedback inhibition shortens the time window for LTD during spike-timing dependent plasticity but not for LTP. We then use a realistic GENESIS model to test two hypothesis about interneuron hypofunction and conclude that a reduction in GAD67 is the most likely candidate as the cause for hypofrontality as observed in Schizophrenia

Optogenetic control of genetically-targeted pyramidal neuron activity in prefrontal cortex

A salient feature of prefrontal cortex organization is the vast diversity of cell types that support the temporal integration of events required for sculpting future responses. A major obstacle in understanding the routing of information among prefrontal neuronal subtypes is the inability to manipulate the electrical activity of genetically defined cell types over behaviorally relevant timescales and activity patterns. To address these constraints, we present here a simple approach for selective activation of prefrontal excitatory neurons in both in vitro and in vivo preparations. Rat prelimbic pyramidal neurons were genetically targeted to express a light-­activated nonselective cation channel, channelrhodopsin-­2, or a light-­driven inward chloride pump, halorhodopsin, which enabled them to be rapidly and reversibly activated or inhibited by pulses of light. These light responsive tools provide a spatially and temporally precise means of studying how different cell types contribute to information processing in cortical circuits. Our customized optrodes and optical commutators for in vivo recording allow for efficient light delivery and recording and can be requested at www.neuro-­cloud.net/nature-precedings/baratta

Learning and discrimination through STDP in a top-down modulated associative memory

This article underlines the learning and discrimination capabilities of a model of associative memory based on artificial networks of spiking neurons. Inspired from neuropsychology and neurobiology, the model implements top-down modulations, as in neocortical layer V pyramidal neurons, with a learning rule based on synaptic plasticity (STDP), for performing a multimodal association learning task. A temporal correlation method of analysis proves the ability of the model to associate specific activity patterns to different samples of stimulation. Even in the absence of initial learning and with continuously varying weights, the activity patterns become stable enough for discrimination