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Mahfooz, K.

Publications and source records attributed to Mahfooz, K..

4 recordsLinked to original sources

Local cortical inhibitory subnetworks are shaped by pyramidal neuron progenitor type

The degree to which cortical neurons share inhibitory synaptic input determines their co-activity within a network. However, the principles by which inhibition is shared between neurons are not known. Here we combine in utero labeling with in vivo two-photon targeted patch-clamp recordings in mature cortex to reveal that a layer 2/3 (L2/3) pyramidal neurons local inhibitory input reflects the embryonic progenitor type from which the neuron is born. In contrast to neighboring neurons, pyramidal neurons derived from intermediate progenitors receive synaptic inhibition that is weakly coupled to local network activity. The underlying mechanisms do not depend upon the amount of inhibitory input received from different interneuron subclasses. Rather, progenitor type defines how much inhibitory input a neuron shares with its neighbors, which is reflected in how individual interneurons target pyramidal neurons according to progenitor type. These findings reveal new significance for progenitor diversity and identify ontogenetic origins of fine-scale inhibitory cortical subnetworks.

neuroscience↗

Cortical integration of higher-order thalamic inputs is lineage-dependent

Primary sensory cortex receives and integrates inputs from first-order and higher-order thalamic nuclei. First-order inputs convey sensory information from the periphery and exhibit simple response properties, whereas higher-order inputs exhibit more complex response properties, provide contextual feedback, and can modulate first-order inputs. Here we show that the way in which cortical neurons integrate these thalamic inputs, reflects the progenitor cell from which the cortical neurons derive. Within layer 4 of mouse primary somatosensory cortex, excitatory neurons that derive from apical intermediate progenitors exhibit multi-whisker response properties and receive higher-order thalamic input, in a manner consistent with their dendritic morphology. These properties depend upon the expression levels of the transcription factor Lhx2, which when increased, abolishes the higher-order properties of apical intermediate progenitor-derived neurons, and disrupts the induction of sensory-evoked plasticity. These data reveal a lineage-dependent mechanism that establishes the integration and functional contribution of higher-order thalamic inputs within cortex.

neuroscience↗

Parallel processing of quickly and slowly mobilized reserve vesicles in hippocampal synapses

Vesicles within presynaptic terminals are thought to be segregated into a variety of readily releasable and reserve pools. The nature of the pools and trafficking between them is not well understood, but pools that are slow to mobilize when synapses are active are often assumed to feed pools that are mobilized more quickly, in a series. However, electrophysiological studies of synaptic transmission have suggested instead a parallel organization where vesicles within slowly and quickly mobilized reserve pools would separately feed independent reluctant- and fast-releasing subdivisions of the readily releasable pool. Here we use FM-dyes to confirm the existence of multiple reserve pools at hippocampal synapses and a parallel organization that prevents intermixing between the pools, even when stimulation is intense enough to drive exocytosis at the maximum rate. The experiments additionally demonstrate extensive heterogeneity among synapses in the relative sizes of the slowly and quickly mobilized reserve pools, which suggests equivalent heterogeneity in the numbers of reluctant and fast-releasing readily releasable vesicles that may be relevant for understanding information processing and storage.

neuroscience↗

Fine-scale excitatory cortical circuits reflect embryonic progenitor pools

Introductory paragraph Introductory paragraph Main text Animals In utero electroporation Intrathalamic injections Slice preparation and recording... Stimulation and recording... Analysis of recordings Histological analyses Statistics Methods Author Contributions References The mammalian neocortex is characterised by precise patterns of synaptic connections, which dictate how information flows through cortical circuits. The degree of convergence and divergence of excitatory information results from highly non-random, short-range and long-range glutamatergic synaptic connections1-11. Previous seminal work has shown that c ...

neuroscience↗